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CELLULAR COMMUNICATION AND SIGNALING-TO
SING THE SONG
 A Presentation by
 Dr. N. Sannigrahi,
 Associate Professor,
 Department of Botany,
 Nistarini College, Purulia (W.B)
 India, 723101
CONTENTS OF THE PRESENTATION
 Cellular Communication:
 General principles of cell communication,
 Cell adhesion and roles of different adhesion molecules,
 gap junctions,
 Different types of Signaling
 Extracellular matrix,
 Integrins,
 Neurotransmission and its regulation
CELL & COMMUNICATION
 Imagine what life would be like if you and the people around you could not
communicate. You would not be able to express your wishes to others, nor could
you ask questions to find out more about your environment. Social organization
is dependent on communication between the individuals that comprise that
society.
 As with people, it is vital for individual cells to be able to interact with their
environment and with each other. This is true whether a cell is growing by itself
in a pond or is one of many cells that form a larger organism. In order to properly
respond to external stimuli, cells have developed complex mechanisms of
communication so that they can receive a message, transfer the information
across the plasma membrane, and then produce changes within the cell in
response to the message.
 So, like the communication of individual to hundreds either emergency or habit,
the cells also need a communication for the sustainability of cell-both for
structure and function
CELL & COMMUNICATION
CELL & COMMUNICATION
 In multicellular organisms, cells constantly send and receive chemical
messages to coordinate the actions of other organs, tissues, and cells. The
ability to send messages quickly and efficiently enables cells to coordinate
and fine-tune their functions.
 While the necessity for cellular communication in larger organisms seems
obvious, even single-celled organisms communicate with each other. Yeast
cells signal each other to aid mating.
 Some forms of bacteria coordinate their actions in order to form large
complexes called biofilms or to organize the production of toxins to remove
competing organisms.
 The ability of cells to communicate through chemical signals originated in
single cells and was essential for the evolution of multicellular organisms.
Efficient, error-free communication is vital for all life.
 So, both the intracellular as well as extracellular communication, both the
signaling cells and the target cells with receptor with ligand with a degree of
specificity becomes operational by different ways.
CELL-CELLADHESION
 The multicellular organisms need interactions within cells and the outside
the cells for its homeostasis and sustainability. The variety of interactions
among the different cells or between cells or cells and their external
environment occur in a selective phenomenon is called cell adhesion.
 The tissues are organized in a tight attachment among themselves in the
multicellular organisms by the phenomenon is called cell-cell- adhesion.
The cell-cell adhesion may or may not be associated with the formation of
structures called cell junctions.
 The cell adhesion may be mediated by – Cell Adhesion Molecules(CAM),
Substratum adhesion molecules and cell junction molecules.
 Cell surface molecules like cell surface proteins either homophilic i.e. like-
bind-like, adhesion between a single type cell or heterophilic adhesion
between cells of different types.
 Five principal classes of CAMs- Cadherins, Immunoglobin super family,
Selectins, Mucins & Integrins
CELL-CELLADHESION
CELL-CELLADHESION
 Ca++ Dependent Homophilic cell-cell adhesion (Cadherins Mediated):
 Cadherins, a family of Ca++ dependent CAMs play a crucial role in cell-cell
adhesion during tissue differentiation.
 40 Different Cadherins-like E,P and N cadherins are mostly expressed,
 These are integral glycoprotein's, 720-750 amino acids, long N-terminal end
is at the extracellular regions, a single transmembrane spanning segment
And a c-terminal cytosolic tail,
 The C-terminal domain is associated with the cytoskeleton, whereas the N-
terminal extracellular domain has repeated sequences bind to Ca++ during
cell-cell adhesion.
 E-cadherins found in the non-neural epithelial tissues-cadherins or
placental cadherins in trophoblasts, N-cadherins are neural cadherins found
in the nervous tissue,
 The extracellular domains contain 113 amino acids having four major
repeats with a recognition terminal site, beside binding, helps in cell sorting
and cell recognition, During cell dimeritization of two recognition terminal
sites is essential between two cells by the cost of Ca++ ions.
CELL-CELLADHESION
 The clustering of cadherins, catenins and actins leads to the formation of a
belt like region called adherins -junction responsible for cell division.
 Cadherins are extremely important for the establishment of cell-cell
adhesion.
 N-CAMs are nerve cell adhesion molecules and play an important role in
differentiation of muscle, glial and nerve cells morphogenesis.
 There are some variants of N-CAM have extra-cellular domain while some
are attached by a glycosylphosphatidyl inositolmolecule to plasma
membrane.
 SELECTINS – Extravasations requires the successive breakage and
formation of cell-cell contacts and this contact is mediated through selectin,
a lectin protein that binds carbohydrate sequences of glycoprotein and
glycolipids,
 The three types of selectins- L, F and P- selectin which are transmembrane
glycoprotein and they play significant role to defend the invasion by the
cell.
CELL JUNCTIONS
 CELL JUNCTIONS- Specialized regions of connections of the matrix
called cell junctions of broadly three types; Occluding junctions, anchoring
junctions and communicating junctions.
 Occluding Junctions: The junction where the cells are prevented from
leaking of even smaller molecules from one side of the sheet to the
otherside.It may be –
 Tight Junctions-thin band of plasma membrane proteins that completely
encircle a polarized cell and are in contact with similar thin bands on
adjacent cells, two integral membrane proteins- occulidin and Claudin are
found in the tight junction perform multiple functions-
 Extracellular fluids surrounding their apical and basolateral membranes are
being separated by tight junctions,
 It acts as barrier that seals off the body cavities such as intestine, stomach
lumen, bile ducts in liver,
 Prevents diffusion of membrane proteins and glycoprotein between apical
and basolateral regions of the plasma membrane.
CELL-CELLADHESION
CELL JUNCTIONS
 ANCHORING JUNCTIONS
 These junctions mechanically attach to the cell’s their cytoskeleton to their
neighbors to extracellular matrix. It may be of the following types-
 Cell to Cell adheren junction- It contains continuous band of Cadherin
molecules usually located near the apical surface just below the tight
junction, provide strong mechanical attachment between cells, help in
animal morphogenesis, folding of epithelial cells into tubes and other
related structures,
 Cell- Cell desmosomal function- Desmosome consists of proteinaceous
adhesion plaques of 15-20 nm thick attached to the cytosolic face of plasma
membranes of adjacent cells and connected by transmembrane linker
proteins. Adhesion is mediated by three transmembranes Ca++ dependent
proteins like desmocollin -I and II identical to classical cadherins.
 Cell matrix : Some anchoring junctions bind the cells to the extracellular
matrix through the integrins that link intracellularity to the actin filaments
called focal adhesion.
CELL JUNCTIONS
 COMMUNICATING JUNCTIONS: These junctions mediate a passage of
chemicals as well as electrical signals from one interacting cell to other by
the followings:
 Gap Junctions & Connections: Almost all the animal tissues , the cells are so
organized that they share a common pool of many small metabolites and
ions that pass freely one cell to another.
 The protein lined channel between adjacent cells that allows passage of ions
and small molecules between the cells is called gap junction.
 It always a maintain a gap of 2 nm-4nm appears as patches between cells
separated by a gap,
 The channels are made up of structures called Connexons,
 Connexons are made up of proteins –connexins containing a central pore
lined by one helix of each connexin,
 When the two such similar channels of two adjoining cells come in contact,
form a gap junction,
 Cadherin may modify the connexin protein and regulates it,
CELL JUNCTIONS
 FUNCTIONS:
i. Gap junction between mammalian cells permit the passage of molecules
but it cannot allows the molecules of mol.wt. 2000 or more like amino
acids, nucleotide phosphates etc. It mainly occur through electrical
coupling or metabolic coupling.
ii. It has been proved that dATP can pass through the channel to the cell
which can not synthesize dATP from DNA,
iii. cAMP and Ca++ can be transferred from cell to cell through the gap
junctions those act as second messenger.
iv. DNA, CN-, Oligomycin etc. inhibit the4 channel function and it confirms
the energy dependence of junction communication,
v. During embryonic development, when cell differentiation takes place
requires diffusion of molecules that can be passed through these channels
, Certain metabolites like nucleotide can pass through the channel.
CELL JUNCTIONS
 PLASMODESMATA AND CELL-CELL COMMUNICATION:
 In plant cells, presence of bridges of cytoplasmic materials that establish
continuity between adjacent cells are called Plasmodesmata that pass through
the thickness of the pectocellulose membrane.
 Depending upon plant type, the density of Plasmodesmata varies 1-10 per sq.
mm,
 In growing meristematic cells, there are more than 1000 such interconnections,
 An extension of the endoplasmic reticulum called desmosome passes through
the ring of the cytosol, the cytoplasmic annulus connecting the adjacent cell
through which molecules pass,
 The Plasmodesmata are rather dynamic structures rapidly altering the
dimensions to allow the transport of bigger molecules,
 Such macromolecules are tracked through the plant cytoplasm with the help of
cytoskeleton that functions as the major tracking system to the site of
Plasmodesmata.
CELL JUNCTIONS
CELL JUNCTIONS
 FUNCTIONS:
 These are open channels that can permit the diffusion of molecules with a
mol. Up to 1000 including proteins, nucleic acids, metabolic products, plant
viruses, signal molecules and some bigger molecules . Soluble molecules
can pass through the cytoplasmic annulus but membrane bound molecules
may pass via desmotubules.
 Movement proteins of plant virus have been discovered which operate an
endogenous Plasmodesmata transport system,
 In maize, during development , outer most L1 layer of meristem does not
transcribe Knl gene but the encoded protein KNL is found in this layer that
confirms the transportation via Plasmodesmata,
 Movement of numerous protein up to mol. Weight 70KD from companion
cell to enucleate sieve tubes of the phloem has been observed through
Plasmodesmata,
FORMS OF SIGNALING
 As per the nature of the cell signaling system, there are four types of
signaling system operational-
 AUTOCRINE- a cell targets itself,
 PARACRINE- signals a near by cell,
 ENDOCRINE- a cell sends the signal to the far off cell through blood
stream
 DIRECT- a cell target a nearby adjoining cell through gap junction.
 Thus, by the above mentioned four cell signaling system, the message for
the execution of the desired work along with the intended action are
mediated by the different mechanisms for sustainability, homeostasis as well
as hormesis.
DIFFERENT TYPES OF SIGNALING
DIFFERENT TYPES OF SIGNALING
 Signals that act locally between cells that are close together are called
paracrine signals. Paracrine signals move by diffusion through the
extracellular matrix . These types of signals usually elicit quick responses
that last only a short amount of time. In order to keep the response localized,
porcine ligand are usually quickly degraded by enzymes or removed by
neighboring cells. Removing the signals reestablishes the concentration
gradient for the signal molecule, allowing them to quickly diffuse through
the intracellular space if released again.
 The paracrine signals found in the different cells in general and neurons in
particular.
 One example of paracrine signaling is the transfer of signals between nerve
cells. The tiny space between nerve cells where signal transmission occurs
is called a synapse. Signals are propagated along nerve cells by fast-moving
electrical impulses. When these impulses reach the end of one nerve cell,
chemical ligand called neurotransmitters are released into the synapse by the
presynaptic cell (the cell emitting the signal).
DIFFERENT TYPES OF SIGNALING
DIFFERENT TYPES OF SIGNALING
DIFFERENT TYPES OF SIGNALING
 The neurotransmitters diffuse across the synapse . The small distance
between nerve cells allows the signal to travel quickly, which enables an
immediate response, such as, “take your hand off the stove!” When the
neurotransmitter binds the receptor on the surface of the postsynaptic cell,
the next electrical impulse is launched. The neurotransmitters are degraded
quickly or are reabsorbed by the presynaptic cell so that the recipient nerve
cell can recover quickly and be prepared to respond rapidly to the next
synaptic signal.
 Thus, the different cell signaling systems play a very significant role for the
coordination of the messages as whenever required for the sound health of
the cell to ensure sustainability of the cell.
DIFFERENT TYPES OF SIGNALING
AUTOCRINE SIGNALING
 When a cell responds to its own signaling molecule, it is called autocrine
signaling (auto = “self”). Autocrine signaling often occurs with other types
of signaling. For example, when a paracrine signal is released, the signaling
cell may respond to the signal along with its neighbors.
 Autocrine signaling often occurs during early development of an organism
to ensure that cells develop into the correct tissues. Autocrine signaling also
regulates pain sensation and inflammatory responses. Further, if a cell is
infected with a virus, the cell can signal itself to undergo programmed cell
death, killing the virus in the process.
ENDOCRINE SIGNALING
 Signals from distant cells are called endocrine signals, and they originate
from endocrine cells. (In the body, many endocrine cells are located in
endocrine glands, such as the thyroid gland, the hypothalamus, and the
pituitary gland.) These types of signals usually produce a slower response
but have a longer-lasting effect. The ligand released in endocrine signaling
are called hormones, signaling molecules that are produced in one part of
the body but affect other body regions some distance away .
 Hormones travel the large distances between endocrine cells and their target
cells via the bloodstream, which is a relatively slow way to move
throughout the body. Because of their form of transport, hormones get
diluted and are present in low concentrations when they act on their target
cells. This is different from paracrine signaling, in which local
concentrations of signaling molecules can be very high.
DIRESCT SIGNALING
 Gap junctions in animals and Plasmodesmata in plants are connections
between the plasma membranes of neighboring cells. These water-filled
channels allow small signaling molecules to diffuse between the two cells.
Small molecules, such as calcium ions (Ca2+), are able to move between
cells, but large molecules like proteins and DNA cannot fit through the
channels. The specificity of the channels ensures that the cells remain
independent but can quickly and easily transmit signals. Direct signaling
allows a group of cells to coordinate their response to a signal that only one
of them may have received. In plants, Plasmodesmata are ubiquitous,
making the entire plant into a giant communication network.
EXTRACELLULAR MATRIX(ECM)
 Cell is a very complex structure and it needs complexity as far as the
structure, function and sustainability is concerned,
 The integrity of the intracellular components and its function is mediated by
cytoskeleton,
 The outside of the cells, there is an urge of interconnectivity as well as
integrity and this is achieved by the extracellular matrix comprising of the
diverse type of proteins and others and 30% of the total proteins are used for
the integrity of the cell as a part of the extracellular matrix.
 A large network of proteins and other molecules that surround, support, and
give structure to cells and tissues in the body. The extracellular matrix helps
cells attach to, and communicate with, nearby cells, and plays an important
role in cell growth, cell movement, and other cell functions.
 It serves as scaffolding of the tissues and organs by the insoluble structural
proteins collagen and elastin and the matrix undergoes profound structural
changes over the time.
EXTRACELLULAR MATRIX(ECM)
EXTRACELLULAR MATRIX(ECM)
ECM has two basic forms-
Basement membrane- ECM between epithelial and stromal layer of cells,
Interstitial matrix- ECM surrounding the cells forms a porous 3D lattice.
 The ECM is a complex mixture of proteins and glycosaminoglycans (a class
of negatively charged polysaccharides). It is composed of three categories
of materials:
 Glycosaminoglycans and their proteoglycans that resist compressive forces
 Adhesive glycoproteins (laminin, fibronectin, tenascin, nidogen)
 Fibrous proteins that provide tensile strength (collagens, elastin).
 The extracellular matrix (ECM) is responsible for the physical maintenance1
of all cells. However, the concept that the ECM has a passive role to play in
cellular activity has been refuted.
 It is now known to play a part in numerous cellular processes including cell
proliferation, differentiation,and migration.
INTEGRINS
 Integrins are the principal receptors used by animal cells to bind to the
extracellular matrix. They are heterodimers and function as transmembrane
linkers between the extracellular matrix and the actin cytoskeleton. A cell
can regulate the adhesive activity of its integrins from within . They are so
called as they integrate the extracellular and intracellular scaffolds named
by Horwiz et al (1986) and Tamkun et al (1986).
 They are the super family of the cell adhesion receptors that bind to the
extracellular matrix ligand, cell surface ligand and soluble ligand.
 They are the transmembrane of αβheterodimers and at least 18 α and 8 β
subunits as found in humans.
 On ligand binding, integrins transduce signals into the cell interior and they
can also receive intracellular signals that regulate their ligand binding
affinity.
 A single β-chain can interact with multiple α chain and thus it can bind to
different legends,
 The largest integrin subfamily is the β1 or very late activation antigen or
VLA integrins.
NEUROTRANSMISSION AND ITS REGULATION
 Neurotransmission is the transmission of chemical messengers called
neurotransmitters . They carry messages from one nerve cell across a space to
the nest nerve, muscle or gland cell. This transmission helps someone to move
limbs, carry sensations, keep heart beating and take in and to receive
information from the different environmental conditions to maintain
homeostasis of the body parts.
 FUNCTIONS OF NERVE AND NEUROTRANSMITTERS:
 Heartbeat and blood pressure,
 Breathing,
 Muscle movements,
 Thought, memory, learning & feelings,
 Sleep, healing and aging,
 Stress response,
 Hormone regulation,
 Digestion, sense of hunger and thrust,
 Senses- like vision, feelings, hearing, taste etc.
NEUROTRANSMISSION AND ITS REGULATION
 HOW DO NEUROTRANSMITTERS WORK?
 The neurotransmitters work with the following three components- A cell
body, axon and axon terminal.
 A Cell Body- vital to produce neurotransmitters and maintain the functions
of nerve cell,
 Axon- Carries electrical signals along the nerve cell to the axon terminal,
 An axon terminal- Here, the electrical message is changed to chemical
signal using neurotransmitters to communicate with the next nerve cell to
the axon terminal,
 Neurotransmitters are located in the axon terminal and stored within the thin
walled sacs called synaptic vesicles that contain thousands of
neurotransmitters molecules.
 Each type of the neurotransmitters lands on and binds to a specific receptor
on the target cell. After binding, the neurotransmitters than triggers a change
in the action of the target cell.
NEUROTRANSMISSION AND ITS REGULATION
NEUROTRANSMISSION AND ITS REGULATION
 ACTION OF NEUROTRANSMITTERS:
 There are three possible ways depending on the specific neurotransmitter:
 EXCITATORY: This neurotransmitter ‘excite’ the neuron and cause it ‘to fire
off’ the messages. The message continues to pass along the next cell by the
neurotransmitters like glutamate, epinephrine and nor-epinephrine.
 INHIBITORY: It blocks or prevent the transmission of the message in the next
cell by the neurotransmitters like GABA or serotonin, Glycine etc.
 MODULATORY: This influences the effects of the other neurotransmitters
and they ‘tweak’ or adjust the others how to send signals to synapse and they
also regulate large numbers of neurons at the same time.
 After sending messages . Neurotransmitters must be cleared off from the
synaptic cleft by the three possible ways- fade away by diffusion, reabsorbed
or reuse by the nerve cell or broken down by the enzyme within the synapse.
DIFFERENE TYPES OF NEUROTRANSMITTERS
 Chemically, the neurotransmitters may be of different types as follows:
 AMINO ACIDS NEUROTRANSMITTERS:
 Glutamate- Excitatory neurotransmitters abundantly present in the brain, plays
a role in cognitive function like thinking, learning , memory; imbalance may
cause Alzheimer's disease, dementia, Parkinson's disease etc.
 Gama Amino Butyric acid (GABA)- Regulate the brain activity to prevent
problems in the areas of anxiety, irritability, concentration, sleep, depression
etc.
 Glycine- control hearing processing, pain transmission and metabolism.
 MONOAMINES NEUROTRANSMITTERS: These neurotransmitters
regulate consciousness, cognition, attention, emotion etc. They are like
serotonin, histamine, dopamine, epinephrine, nor-epinephrine, Dysfunctions of
the compounds may create problems like seasonal; affective disorders, anxiety.
Depression by serotonin, asthma, bronchoplasm, multiple sclerosis by etc by
Histamine, Schizophrenia, bipolar disorder, restless legs syndrome, attention
deficit by Dopamine, too much epinephrine may lead to high blood pressure,
DIFFERENE TYPES OF NEUROTRANSMITTERS
NEUROTRANSMISSION AND ITS REGULATION
 PEPTIDE NEUROTRANSMITTERS:
 Endorphins: It is a pain reliever and play a role in the perception of pain,
releases of endorphins reduces pain, have ‘feel good’ feelings, low level of this
compound may cause fibromyalgia and other types of headache.
 ACETYLCHOLINE: This excitatory neurotransmitter play a multiple role in
the central nervous system(CNS) like brain and spinal cord; released by the
most neurons of autonomic nervous system (ANS) regulating heart rate, blood
pressure and gut motility.
 It plays a significant role in the different physiological functions of the body
like muscle contraction, memory, motivation, sexual desire, sleep and learning
etc.
 Imbalances may cause a number of issues like Alzheimer's disease, Seizures
and Muscle spasms etc.
NEUROTRANSMISSION AND ITS REGULATION
NEUROTRANSMISSION AND ITS REGULATION
 Neurotransmission is regulated by several different factors:
 the availability and rate-of-synthesis of the neurotransmitter,
 the release of that neurotransmitter,
 the baseline activity of the postsynaptic cell,
 the number of available postsynaptic receptors for the neurotransmitter to bind
to, and the subsequent.
 The rate of the precursor synthesis or precursor uptake or transmitter uptake,
 Activity of the regulatory enzymes for its biosynthesis, processing or
breakdown
 To ensure these functions, the neuron responds to the signals-
i. Obtained from the post synaptic receptor activation or blockade,
ii. Generated within or at presynaptic sites (Rs, R3, R4). The DNA plays a
crucial role in this regard.
Beauty lies in the eyes of the beholder”- Plato
THANKS FOR YOUR HAPPINESS
 ACKNOWLEDGEMENT:
 Cell and Molecular Biology- Ajoy Paul,
 National Institute of Health website,
 Khan Academy,
 Google for images,
 Different web pages for the content,
 Different others for directly or indirectly associated with this presentation.
 Disclaimer:
 This presentation has been developed for the academic fraternity as a part of
the enrichment of online study materials without any kind of financial
interest. If somebody have the pleasure of happiness, the author will be
grateful to far off friends.

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Cellular Communication and regulation of communication mechanisms to sing the song of the cell.

  • 1. CELLULAR COMMUNICATION AND SIGNALING-TO SING THE SONG  A Presentation by  Dr. N. Sannigrahi,  Associate Professor,  Department of Botany,  Nistarini College, Purulia (W.B)  India, 723101
  • 2. CONTENTS OF THE PRESENTATION  Cellular Communication:  General principles of cell communication,  Cell adhesion and roles of different adhesion molecules,  gap junctions,  Different types of Signaling  Extracellular matrix,  Integrins,  Neurotransmission and its regulation
  • 3. CELL & COMMUNICATION  Imagine what life would be like if you and the people around you could not communicate. You would not be able to express your wishes to others, nor could you ask questions to find out more about your environment. Social organization is dependent on communication between the individuals that comprise that society.  As with people, it is vital for individual cells to be able to interact with their environment and with each other. This is true whether a cell is growing by itself in a pond or is one of many cells that form a larger organism. In order to properly respond to external stimuli, cells have developed complex mechanisms of communication so that they can receive a message, transfer the information across the plasma membrane, and then produce changes within the cell in response to the message.  So, like the communication of individual to hundreds either emergency or habit, the cells also need a communication for the sustainability of cell-both for structure and function
  • 5. CELL & COMMUNICATION  In multicellular organisms, cells constantly send and receive chemical messages to coordinate the actions of other organs, tissues, and cells. The ability to send messages quickly and efficiently enables cells to coordinate and fine-tune their functions.  While the necessity for cellular communication in larger organisms seems obvious, even single-celled organisms communicate with each other. Yeast cells signal each other to aid mating.  Some forms of bacteria coordinate their actions in order to form large complexes called biofilms or to organize the production of toxins to remove competing organisms.  The ability of cells to communicate through chemical signals originated in single cells and was essential for the evolution of multicellular organisms. Efficient, error-free communication is vital for all life.  So, both the intracellular as well as extracellular communication, both the signaling cells and the target cells with receptor with ligand with a degree of specificity becomes operational by different ways.
  • 6. CELL-CELLADHESION  The multicellular organisms need interactions within cells and the outside the cells for its homeostasis and sustainability. The variety of interactions among the different cells or between cells or cells and their external environment occur in a selective phenomenon is called cell adhesion.  The tissues are organized in a tight attachment among themselves in the multicellular organisms by the phenomenon is called cell-cell- adhesion. The cell-cell adhesion may or may not be associated with the formation of structures called cell junctions.  The cell adhesion may be mediated by – Cell Adhesion Molecules(CAM), Substratum adhesion molecules and cell junction molecules.  Cell surface molecules like cell surface proteins either homophilic i.e. like- bind-like, adhesion between a single type cell or heterophilic adhesion between cells of different types.  Five principal classes of CAMs- Cadherins, Immunoglobin super family, Selectins, Mucins & Integrins
  • 8. CELL-CELLADHESION  Ca++ Dependent Homophilic cell-cell adhesion (Cadherins Mediated):  Cadherins, a family of Ca++ dependent CAMs play a crucial role in cell-cell adhesion during tissue differentiation.  40 Different Cadherins-like E,P and N cadherins are mostly expressed,  These are integral glycoprotein's, 720-750 amino acids, long N-terminal end is at the extracellular regions, a single transmembrane spanning segment And a c-terminal cytosolic tail,  The C-terminal domain is associated with the cytoskeleton, whereas the N- terminal extracellular domain has repeated sequences bind to Ca++ during cell-cell adhesion.  E-cadherins found in the non-neural epithelial tissues-cadherins or placental cadherins in trophoblasts, N-cadherins are neural cadherins found in the nervous tissue,  The extracellular domains contain 113 amino acids having four major repeats with a recognition terminal site, beside binding, helps in cell sorting and cell recognition, During cell dimeritization of two recognition terminal sites is essential between two cells by the cost of Ca++ ions.
  • 9. CELL-CELLADHESION  The clustering of cadherins, catenins and actins leads to the formation of a belt like region called adherins -junction responsible for cell division.  Cadherins are extremely important for the establishment of cell-cell adhesion.  N-CAMs are nerve cell adhesion molecules and play an important role in differentiation of muscle, glial and nerve cells morphogenesis.  There are some variants of N-CAM have extra-cellular domain while some are attached by a glycosylphosphatidyl inositolmolecule to plasma membrane.  SELECTINS – Extravasations requires the successive breakage and formation of cell-cell contacts and this contact is mediated through selectin, a lectin protein that binds carbohydrate sequences of glycoprotein and glycolipids,  The three types of selectins- L, F and P- selectin which are transmembrane glycoprotein and they play significant role to defend the invasion by the cell.
  • 10. CELL JUNCTIONS  CELL JUNCTIONS- Specialized regions of connections of the matrix called cell junctions of broadly three types; Occluding junctions, anchoring junctions and communicating junctions.  Occluding Junctions: The junction where the cells are prevented from leaking of even smaller molecules from one side of the sheet to the otherside.It may be –  Tight Junctions-thin band of plasma membrane proteins that completely encircle a polarized cell and are in contact with similar thin bands on adjacent cells, two integral membrane proteins- occulidin and Claudin are found in the tight junction perform multiple functions-  Extracellular fluids surrounding their apical and basolateral membranes are being separated by tight junctions,  It acts as barrier that seals off the body cavities such as intestine, stomach lumen, bile ducts in liver,  Prevents diffusion of membrane proteins and glycoprotein between apical and basolateral regions of the plasma membrane.
  • 12. CELL JUNCTIONS  ANCHORING JUNCTIONS  These junctions mechanically attach to the cell’s their cytoskeleton to their neighbors to extracellular matrix. It may be of the following types-  Cell to Cell adheren junction- It contains continuous band of Cadherin molecules usually located near the apical surface just below the tight junction, provide strong mechanical attachment between cells, help in animal morphogenesis, folding of epithelial cells into tubes and other related structures,  Cell- Cell desmosomal function- Desmosome consists of proteinaceous adhesion plaques of 15-20 nm thick attached to the cytosolic face of plasma membranes of adjacent cells and connected by transmembrane linker proteins. Adhesion is mediated by three transmembranes Ca++ dependent proteins like desmocollin -I and II identical to classical cadherins.  Cell matrix : Some anchoring junctions bind the cells to the extracellular matrix through the integrins that link intracellularity to the actin filaments called focal adhesion.
  • 13. CELL JUNCTIONS  COMMUNICATING JUNCTIONS: These junctions mediate a passage of chemicals as well as electrical signals from one interacting cell to other by the followings:  Gap Junctions & Connections: Almost all the animal tissues , the cells are so organized that they share a common pool of many small metabolites and ions that pass freely one cell to another.  The protein lined channel between adjacent cells that allows passage of ions and small molecules between the cells is called gap junction.  It always a maintain a gap of 2 nm-4nm appears as patches between cells separated by a gap,  The channels are made up of structures called Connexons,  Connexons are made up of proteins –connexins containing a central pore lined by one helix of each connexin,  When the two such similar channels of two adjoining cells come in contact, form a gap junction,  Cadherin may modify the connexin protein and regulates it,
  • 14. CELL JUNCTIONS  FUNCTIONS: i. Gap junction between mammalian cells permit the passage of molecules but it cannot allows the molecules of mol.wt. 2000 or more like amino acids, nucleotide phosphates etc. It mainly occur through electrical coupling or metabolic coupling. ii. It has been proved that dATP can pass through the channel to the cell which can not synthesize dATP from DNA, iii. cAMP and Ca++ can be transferred from cell to cell through the gap junctions those act as second messenger. iv. DNA, CN-, Oligomycin etc. inhibit the4 channel function and it confirms the energy dependence of junction communication, v. During embryonic development, when cell differentiation takes place requires diffusion of molecules that can be passed through these channels , Certain metabolites like nucleotide can pass through the channel.
  • 15. CELL JUNCTIONS  PLASMODESMATA AND CELL-CELL COMMUNICATION:  In plant cells, presence of bridges of cytoplasmic materials that establish continuity between adjacent cells are called Plasmodesmata that pass through the thickness of the pectocellulose membrane.  Depending upon plant type, the density of Plasmodesmata varies 1-10 per sq. mm,  In growing meristematic cells, there are more than 1000 such interconnections,  An extension of the endoplasmic reticulum called desmosome passes through the ring of the cytosol, the cytoplasmic annulus connecting the adjacent cell through which molecules pass,  The Plasmodesmata are rather dynamic structures rapidly altering the dimensions to allow the transport of bigger molecules,  Such macromolecules are tracked through the plant cytoplasm with the help of cytoskeleton that functions as the major tracking system to the site of Plasmodesmata.
  • 17. CELL JUNCTIONS  FUNCTIONS:  These are open channels that can permit the diffusion of molecules with a mol. Up to 1000 including proteins, nucleic acids, metabolic products, plant viruses, signal molecules and some bigger molecules . Soluble molecules can pass through the cytoplasmic annulus but membrane bound molecules may pass via desmotubules.  Movement proteins of plant virus have been discovered which operate an endogenous Plasmodesmata transport system,  In maize, during development , outer most L1 layer of meristem does not transcribe Knl gene but the encoded protein KNL is found in this layer that confirms the transportation via Plasmodesmata,  Movement of numerous protein up to mol. Weight 70KD from companion cell to enucleate sieve tubes of the phloem has been observed through Plasmodesmata,
  • 18. FORMS OF SIGNALING  As per the nature of the cell signaling system, there are four types of signaling system operational-  AUTOCRINE- a cell targets itself,  PARACRINE- signals a near by cell,  ENDOCRINE- a cell sends the signal to the far off cell through blood stream  DIRECT- a cell target a nearby adjoining cell through gap junction.  Thus, by the above mentioned four cell signaling system, the message for the execution of the desired work along with the intended action are mediated by the different mechanisms for sustainability, homeostasis as well as hormesis.
  • 19. DIFFERENT TYPES OF SIGNALING
  • 20. DIFFERENT TYPES OF SIGNALING  Signals that act locally between cells that are close together are called paracrine signals. Paracrine signals move by diffusion through the extracellular matrix . These types of signals usually elicit quick responses that last only a short amount of time. In order to keep the response localized, porcine ligand are usually quickly degraded by enzymes or removed by neighboring cells. Removing the signals reestablishes the concentration gradient for the signal molecule, allowing them to quickly diffuse through the intracellular space if released again.  The paracrine signals found in the different cells in general and neurons in particular.  One example of paracrine signaling is the transfer of signals between nerve cells. The tiny space between nerve cells where signal transmission occurs is called a synapse. Signals are propagated along nerve cells by fast-moving electrical impulses. When these impulses reach the end of one nerve cell, chemical ligand called neurotransmitters are released into the synapse by the presynaptic cell (the cell emitting the signal).
  • 21. DIFFERENT TYPES OF SIGNALING
  • 22. DIFFERENT TYPES OF SIGNALING
  • 23. DIFFERENT TYPES OF SIGNALING  The neurotransmitters diffuse across the synapse . The small distance between nerve cells allows the signal to travel quickly, which enables an immediate response, such as, “take your hand off the stove!” When the neurotransmitter binds the receptor on the surface of the postsynaptic cell, the next electrical impulse is launched. The neurotransmitters are degraded quickly or are reabsorbed by the presynaptic cell so that the recipient nerve cell can recover quickly and be prepared to respond rapidly to the next synaptic signal.  Thus, the different cell signaling systems play a very significant role for the coordination of the messages as whenever required for the sound health of the cell to ensure sustainability of the cell.
  • 24. DIFFERENT TYPES OF SIGNALING
  • 25. AUTOCRINE SIGNALING  When a cell responds to its own signaling molecule, it is called autocrine signaling (auto = “self”). Autocrine signaling often occurs with other types of signaling. For example, when a paracrine signal is released, the signaling cell may respond to the signal along with its neighbors.  Autocrine signaling often occurs during early development of an organism to ensure that cells develop into the correct tissues. Autocrine signaling also regulates pain sensation and inflammatory responses. Further, if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process.
  • 26. ENDOCRINE SIGNALING  Signals from distant cells are called endocrine signals, and they originate from endocrine cells. (In the body, many endocrine cells are located in endocrine glands, such as the thyroid gland, the hypothalamus, and the pituitary gland.) These types of signals usually produce a slower response but have a longer-lasting effect. The ligand released in endocrine signaling are called hormones, signaling molecules that are produced in one part of the body but affect other body regions some distance away .  Hormones travel the large distances between endocrine cells and their target cells via the bloodstream, which is a relatively slow way to move throughout the body. Because of their form of transport, hormones get diluted and are present in low concentrations when they act on their target cells. This is different from paracrine signaling, in which local concentrations of signaling molecules can be very high.
  • 27. DIRESCT SIGNALING  Gap junctions in animals and Plasmodesmata in plants are connections between the plasma membranes of neighboring cells. These water-filled channels allow small signaling molecules to diffuse between the two cells. Small molecules, such as calcium ions (Ca2+), are able to move between cells, but large molecules like proteins and DNA cannot fit through the channels. The specificity of the channels ensures that the cells remain independent but can quickly and easily transmit signals. Direct signaling allows a group of cells to coordinate their response to a signal that only one of them may have received. In plants, Plasmodesmata are ubiquitous, making the entire plant into a giant communication network.
  • 28. EXTRACELLULAR MATRIX(ECM)  Cell is a very complex structure and it needs complexity as far as the structure, function and sustainability is concerned,  The integrity of the intracellular components and its function is mediated by cytoskeleton,  The outside of the cells, there is an urge of interconnectivity as well as integrity and this is achieved by the extracellular matrix comprising of the diverse type of proteins and others and 30% of the total proteins are used for the integrity of the cell as a part of the extracellular matrix.  A large network of proteins and other molecules that surround, support, and give structure to cells and tissues in the body. The extracellular matrix helps cells attach to, and communicate with, nearby cells, and plays an important role in cell growth, cell movement, and other cell functions.  It serves as scaffolding of the tissues and organs by the insoluble structural proteins collagen and elastin and the matrix undergoes profound structural changes over the time.
  • 30. EXTRACELLULAR MATRIX(ECM) ECM has two basic forms- Basement membrane- ECM between epithelial and stromal layer of cells, Interstitial matrix- ECM surrounding the cells forms a porous 3D lattice.  The ECM is a complex mixture of proteins and glycosaminoglycans (a class of negatively charged polysaccharides). It is composed of three categories of materials:  Glycosaminoglycans and their proteoglycans that resist compressive forces  Adhesive glycoproteins (laminin, fibronectin, tenascin, nidogen)  Fibrous proteins that provide tensile strength (collagens, elastin).  The extracellular matrix (ECM) is responsible for the physical maintenance1 of all cells. However, the concept that the ECM has a passive role to play in cellular activity has been refuted.  It is now known to play a part in numerous cellular processes including cell proliferation, differentiation,and migration.
  • 31. INTEGRINS  Integrins are the principal receptors used by animal cells to bind to the extracellular matrix. They are heterodimers and function as transmembrane linkers between the extracellular matrix and the actin cytoskeleton. A cell can regulate the adhesive activity of its integrins from within . They are so called as they integrate the extracellular and intracellular scaffolds named by Horwiz et al (1986) and Tamkun et al (1986).  They are the super family of the cell adhesion receptors that bind to the extracellular matrix ligand, cell surface ligand and soluble ligand.  They are the transmembrane of αβheterodimers and at least 18 α and 8 β subunits as found in humans.  On ligand binding, integrins transduce signals into the cell interior and they can also receive intracellular signals that regulate their ligand binding affinity.  A single β-chain can interact with multiple α chain and thus it can bind to different legends,  The largest integrin subfamily is the β1 or very late activation antigen or VLA integrins.
  • 32. NEUROTRANSMISSION AND ITS REGULATION  Neurotransmission is the transmission of chemical messengers called neurotransmitters . They carry messages from one nerve cell across a space to the nest nerve, muscle or gland cell. This transmission helps someone to move limbs, carry sensations, keep heart beating and take in and to receive information from the different environmental conditions to maintain homeostasis of the body parts.  FUNCTIONS OF NERVE AND NEUROTRANSMITTERS:  Heartbeat and blood pressure,  Breathing,  Muscle movements,  Thought, memory, learning & feelings,  Sleep, healing and aging,  Stress response,  Hormone regulation,  Digestion, sense of hunger and thrust,  Senses- like vision, feelings, hearing, taste etc.
  • 33. NEUROTRANSMISSION AND ITS REGULATION  HOW DO NEUROTRANSMITTERS WORK?  The neurotransmitters work with the following three components- A cell body, axon and axon terminal.  A Cell Body- vital to produce neurotransmitters and maintain the functions of nerve cell,  Axon- Carries electrical signals along the nerve cell to the axon terminal,  An axon terminal- Here, the electrical message is changed to chemical signal using neurotransmitters to communicate with the next nerve cell to the axon terminal,  Neurotransmitters are located in the axon terminal and stored within the thin walled sacs called synaptic vesicles that contain thousands of neurotransmitters molecules.  Each type of the neurotransmitters lands on and binds to a specific receptor on the target cell. After binding, the neurotransmitters than triggers a change in the action of the target cell.
  • 35. NEUROTRANSMISSION AND ITS REGULATION  ACTION OF NEUROTRANSMITTERS:  There are three possible ways depending on the specific neurotransmitter:  EXCITATORY: This neurotransmitter ‘excite’ the neuron and cause it ‘to fire off’ the messages. The message continues to pass along the next cell by the neurotransmitters like glutamate, epinephrine and nor-epinephrine.  INHIBITORY: It blocks or prevent the transmission of the message in the next cell by the neurotransmitters like GABA or serotonin, Glycine etc.  MODULATORY: This influences the effects of the other neurotransmitters and they ‘tweak’ or adjust the others how to send signals to synapse and they also regulate large numbers of neurons at the same time.  After sending messages . Neurotransmitters must be cleared off from the synaptic cleft by the three possible ways- fade away by diffusion, reabsorbed or reuse by the nerve cell or broken down by the enzyme within the synapse.
  • 36. DIFFERENE TYPES OF NEUROTRANSMITTERS  Chemically, the neurotransmitters may be of different types as follows:  AMINO ACIDS NEUROTRANSMITTERS:  Glutamate- Excitatory neurotransmitters abundantly present in the brain, plays a role in cognitive function like thinking, learning , memory; imbalance may cause Alzheimer's disease, dementia, Parkinson's disease etc.  Gama Amino Butyric acid (GABA)- Regulate the brain activity to prevent problems in the areas of anxiety, irritability, concentration, sleep, depression etc.  Glycine- control hearing processing, pain transmission and metabolism.  MONOAMINES NEUROTRANSMITTERS: These neurotransmitters regulate consciousness, cognition, attention, emotion etc. They are like serotonin, histamine, dopamine, epinephrine, nor-epinephrine, Dysfunctions of the compounds may create problems like seasonal; affective disorders, anxiety. Depression by serotonin, asthma, bronchoplasm, multiple sclerosis by etc by Histamine, Schizophrenia, bipolar disorder, restless legs syndrome, attention deficit by Dopamine, too much epinephrine may lead to high blood pressure,
  • 37. DIFFERENE TYPES OF NEUROTRANSMITTERS
  • 38. NEUROTRANSMISSION AND ITS REGULATION  PEPTIDE NEUROTRANSMITTERS:  Endorphins: It is a pain reliever and play a role in the perception of pain, releases of endorphins reduces pain, have ‘feel good’ feelings, low level of this compound may cause fibromyalgia and other types of headache.  ACETYLCHOLINE: This excitatory neurotransmitter play a multiple role in the central nervous system(CNS) like brain and spinal cord; released by the most neurons of autonomic nervous system (ANS) regulating heart rate, blood pressure and gut motility.  It plays a significant role in the different physiological functions of the body like muscle contraction, memory, motivation, sexual desire, sleep and learning etc.  Imbalances may cause a number of issues like Alzheimer's disease, Seizures and Muscle spasms etc.
  • 40. NEUROTRANSMISSION AND ITS REGULATION  Neurotransmission is regulated by several different factors:  the availability and rate-of-synthesis of the neurotransmitter,  the release of that neurotransmitter,  the baseline activity of the postsynaptic cell,  the number of available postsynaptic receptors for the neurotransmitter to bind to, and the subsequent.  The rate of the precursor synthesis or precursor uptake or transmitter uptake,  Activity of the regulatory enzymes for its biosynthesis, processing or breakdown  To ensure these functions, the neuron responds to the signals- i. Obtained from the post synaptic receptor activation or blockade, ii. Generated within or at presynaptic sites (Rs, R3, R4). The DNA plays a crucial role in this regard.
  • 41. Beauty lies in the eyes of the beholder”- Plato
  • 42. THANKS FOR YOUR HAPPINESS  ACKNOWLEDGEMENT:  Cell and Molecular Biology- Ajoy Paul,  National Institute of Health website,  Khan Academy,  Google for images,  Different web pages for the content,  Different others for directly or indirectly associated with this presentation.  Disclaimer:  This presentation has been developed for the academic fraternity as a part of the enrichment of online study materials without any kind of financial interest. If somebody have the pleasure of happiness, the author will be grateful to far off friends.