The Cell signalling is part of any communication process that governs basic activities of cells and coordinates all cell actions.
The ability of cells to perceive and correctly respond to their microenvironment is the basis of development,tissue repair, immunity, tissue homeostasis.
The cell membrane receptors and internal receptors have been discussed along with current trends in cell signalling.
1. Visualization of cell signalling
2. Stem cells and cell signalling
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CELL SIGNALLING: Mechanism and Current trends
1. Cell Signalling
Mechanism and Current Trends
BIT1004: Cell Biology and Biochemistry
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2. C O NTE NTS
• Introduction
• Modes of cell signaling
• Communication between cells
• Signal transduction
• Ion channels
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3. INTRODUCTION
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• Cell signalling is part of any communication process that governs basic
activities of cells and coordinates all cell actions.
• The ability of cells to perceive and correctly respond to their
microenvironment is the basis of:
-Development
-Tissue repair
-Immunity
-Tissue homeostasis.
• Errors in signaling interactions and cellular information processing are
responsible for diseases such as:
-Cancer
-Autoimmunity
-Diabetes
• By understanding cell signaling, diseases may be treated more
effectively and, theoretically, artificial tissues may be created.
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4. CELL SIGNALING
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• Cell signaling has been most extensively studied in the context of human
diseases and signaling between cells of a single organism.
• It may also occur between the cells of two different organisms.
• In many mammals, early embryo cells exchange signals with cells of the
uterus.
• In the human gastrointestinal tract, bacteria exchange signals with each
other and with human epithelial and immune system cells.
• For the yeast Saccharomyces cerevisiae during mating, some cells send a
peptide signal (mating factor pheromones) into their environment.
• The mating factor peptide may bind to a cell surface receptor on other
yeast cells and induce them to prepare for mating.[9]
5. SIGNAL TRANSDUCTTION
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• Signal transduction is the process by which a chemical or physical signal is
transmitted through a cell as a series of molecular events( most commonly
protein phosphorylation catalyzed by protein kinases).
• Proteins responsible for detecting stimuli are generally termed receptors.
• The changes elicited by ligand binding (or signal sensing) in a receptor give rise
to a signaling cascade, which is a chain of biochemical events along a signaling
pathway.
• When signaling pathways interact with one another they form networks, which
allow cellular responses to be coordinated, often by combinatorial signaling
events.
• At the molecular level, such responses include changes in the:
-Transcription or translation of genes
-Post-translational and conformational changes in protein
-Changes in proteinlocation.
8. SYNTHESIS OF SIGNALLING
MOLECULES
RELEASE OF SIGNALLING MOLECULES
TRANSPORT OF SIGNAL TO TARGET CELLS
DETECTION & BINDING OF SIGNAL BY SPECIFIC RECEPTOR
CHANGES DUE TO RECEPTOR-SIGNAL COMPLEX
SIGNAL REMOVAL
RESPNOSE TERMINATION
STEPS IN CELL SIGNALING
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9. CLASSIFICATION OF INTERCELLULAR
COMMUNICATION
Intercellular signaling is subdivided into the following classifications:
• Autocrine: signals target the cell itself. Sometimes autocrine cells can
target cells close by if they are the same type of cell as the emitting cell.
An example of this are immune cells.
• Paracrine: signals target cells in the vicinity of the emitting cell.
neurotransmitters represent an example.
• Endocrine: signals target distant cells. Endocrine cells produce
hormones that travel through the blood to reach all parts of the body.
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CELL SURFACE RECEPTORS
Cell surface receptors can be separated into 4 categories on basis of
their mechanism of action:
- G- Protein linked receptors (GPCRs)
- Ion Channel Receptors
- Receptors lacking intrinsic catalytic activity but direct
association with cytoplasmic protein tyrosine kinase
- Receptors with intrinsic enzymatic activities
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INTRACELLULAR RECEPTORS
• Intracellular receptors are present inside of cell.
• Classic hormones that use intracellular receptors include
thyroid and steroid hormones.
• Examples are the class of nuclear receptors located in the
cell nucleus and cytoplasm and the IP3 receptor located on
the endoplasmic reticulum.
• The ligands that bind to them are usually intracellular second
messengers like inositol trisphosphate (IP3) and extracellular
lipophilic hormones like steroid hormones.
• Some intracrine peptide hormones also have intracellular
receptors.,
24. 1. VISUALIZING CELL SIGNALLING
• Techniques for the study of intracellular ions are used widely in biology, including
for the tracking of calcium waves or ions affecting pH within living cells.
• The ability to monitor changes in intracellular ion concentrations over time is vital
• Ion channels that span the outer cell membrane open or close in response to
extracellular and intracellular signals, potentially altering how the cell behaves.
• These fluctuations can be visualized and quantified using ratiometric microscopy
and special fluorescent dyes designed to bind specific ions, such as the FURA-2
indicator dye specific to calcium ions.
• Changes in the photophysics of the dye as it binds to its target ion allows for
quantitation of the bound and unbound ratio, and thus the concentration of the
ion under investigation.
CURRENT TRENDS
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25. • GFP-based kinase reporters that phase-separate upon kinase activation via
multivalent protein-protein interactions, forming intensively fluorescent droplets.
Called SPARK (separation of phases-based activity reporter of kinase)
• These reporters have large dynamic range (fluorescence change), high
brightness, fast kinetics, and are reversible. The SPARK-based protein kinase A
(PKA) reporter reveals oscillatory dynamics of PKA activities upon G protein-
coupled receptor activation.
• The SPARK-based extracellular signal-regulated kinase (ERK) reporter unveils
transient dynamics of ERK activity during tracheal metamorphosis in live
Drosophila.
• Because of intensive brightness and simple signal pattern, SPARKs allow easy
examination of kinase signaling in living animals in a qualitative way. The
modular design of SPARK will facilitate development of reporters of other
kinases.
CURRENT TRENDS
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26. 2. STEM CELLS
• Stem cells are undifferentiaied cell that can differentiate and give rise to different
kind of cells.
• Stem cells are responsible for proper development of body, tissue repair and
growth.
• These cells are complicated in types of cancers
• They have unlimited potential to cure many diseases
• IPSC's are induced pluripotent stem cell that are artifically created from
differentiated cell by dedifferentiation
• IPSC's are used to treat tissue disorders, cataract and other diseases,
• Cell signals that maintain stemness of a factor are being extensively studied.
CURRENT TRENDS
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27. • Cytokine-dependent activation of STAT3 drives ES cell self-renewal
• ERKs antagonize ES cell self-renewal
• PI3K signalling in ES cell propagation
• An increased amount of 3′-phosphorylated phosphoinositides is frequently
associated with growth factor and cytokine signalling pathways.
• Unique signalling adaptors in ES cells
-Embryonic stem cells express a variant of SH2-containing inositol 5′-
phosphatase (SHIP) that lacks the SH2 domain This enzyme normally
removes 5′ phosphates from the lipid products of PI3K, and in some
systems it inhibits the activation of downstream signals such as PKB.
-Embryonic stem cells also specifically express large amounts of a variant
Gab1 molecule. This protein lacks the N-terminal PH domain, which results
in attenuated coupling to the Ras/ERK cascade .
• Cell-cycle control differs in differentiated cells and ES cells
CURRENT TRENDS
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