Cell Signal transduction and its importance in various cell and tissue-led activities.

1. MADRAS CHRISTIAN COLLEGE ( AUTONOMOUS) , CHENNAI
Presentation On
Cell Signal Transduction
Presented By:
Alok Kumar

2. What is Cell Signaling ?
Cell signaling, which is also often referred to as signal transduction or
transmembrane signaling, is the process by which cells communicate
with their environment and respond temporally to external cues that
they sense there.
There are numerous pathways in cell communication or cell signaling.
Their pathways rarely are linear. Most of the pathways consist degree
of complex matrix .
Noting happens in a cell without proper signaling , unicellular organisms
are autonomous usually but they might get signals from environment
while in multicellular organism , cells are getting signals from neighbor
cells also.

3. Brief History About Cell Signaling Research :-
The discovery of cellular signaling dates back to 1855 when Claude Bernard described
how certain ‘internal secretions’ of ductless glands, released into the bloodstream, can
have effects on distant cells.
Around 1880, British naturalist Charles Darwin and his son Francis Darwin discovered
a similar phenomenon of phototropism of coleoptile (shoot tips) in plants and inferred
“Some influence is transmitted from the tip to the more basal regions of the shoot there-
by regulating growth and inducing curvature”. This transmittable factor or messenger was
later termed as auxin.
A few years later, John Langley and his student Thomas Elliott discovered a ‘receptive
substance’ or receptors while studying sympathetic neuro-effector transmission.

4. Later in 1905, Ernest Starling first coined the word ‘hormone’ to explain, “The chemical
messengers which spread from cell to cell along the bloodstream, may coordinate the
activities and growth of different parts of the body”. Following the discoveries of the
messengers and receptors, the downstream intracellular events started unfolding during
the 1950s. Rita Levi-Montalcini discovered that tumor extracts can cause neurite out
growth and identified the factor as the nerve growth factor .
The word ‘signal transduction’ appeared in biological literature in the 1970s, further
elucidation of which was provided by Martin Rodbell in 1980 who postulated that
‘individual cells were cybernetic systems made up of three distinct molecular com-
ponents: discriminators, transducers and amplifiers.’ The cell receptors are the
discriminators that receive external signals and process this information across the
cell membrane via the cellular transducers.

5. Types Of Cell Signaling :-
Mainly we can classify cell signal transduction in two big categories –
1. Intracellular Signal Transduction
2. Extracellular Signal Transduction
Chain of reactions transmits signals from the cell surface to a variety of intracellular targets, is known as
Intracellular Signal Transduction. Intracellular signaling pathways thus connect the cell surface to the nucleus,
leading to changes in gene expression in response to extracellular stimuli.
Extracellular signaling molecules regulate interaction between unicellular organisms and are critical regulators
of physiology and development in multicellular organisms. In multicellular organisms , extra cellular signaling
can be induced by neighboring cell or foreign stimuli .

6. Components Of Cell Signal Transduction:-
 Ligands or Signals
 Receptors
 Specificity
 Signaling Domain
 Transducers
 Second Messengers
 Transcriptional Factors
Resource : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651758/

7.  Ligand Or Signal :-
 Signals are perturbations of cellular homeostasis and cells mainly respond to
Mechanical (mechanotransduction),
Electrical (electrotransduction), or
Chemical (chemotransduction) stimuli.
 In biology, the majority of the signals are chemical in nature. For example, prokaryotic cells have sensors that
detect nutrients and mediate mechanotransduction towards higher nutrient gradients.
 Similarly, eukaryotic cells also have sophisticated ways of responding to signals such as growth factors,
hormones, cytokines, neurotransmitters, extracellular matrix components etc.

9.  Receptors :-
 There are two broad categories of receptors cell-surface (Extracellular) receptors and intracellular receptors.
 Cell-surface receptors span the plasma membrane and have distinct extracellular ligand binding domain.
 Upon ligand binding, the membrane-spanning receptors undergo a conformational change in their
extracellular domain and activate the cytoplasmic domain-linked enzymatic machinery, usually kinases,
phosphatases, and adaptors. Cell-surface receptors can be categorized into G-protein coupled receptors,
ionotropic receptors.
 Intracellular receptors may be nuclear receptors (for e.g., androgen receptor, estrogen receptor, cytoplasmic
receptors, or organellar receptors like in mitochondria, endoplasmic reticulum (ER), and Golgi apparatus that
bind to small lipophilic molecules, which cross the plasma membrane.
 Sigma receptors are found to be associated with the ER membrane and act as a chaperone to stabilize ER
membrane proteins like IP3 receptor.

10. We can classify all receptors in following types:-
 Type -1 ( ligand gated Ion Channel )
[Time scale – Milli-seconds]
 Type-2 ( G- protein coupled receptors)
[Time scale – Seconds]
 Type-3 ( Enzyme linked receptors)
[Time scale –Hours]
 Type-4 ( Nuclear receptors )
[Time scale –Days ]

11.  Specificity :-
 Receptors exhibit a high binding affinity for their specific ligands, for example insulin receptor has a high
binding affinity for only insulin, conferring specificity to signaling.
 Varying cell types might have a different number and type of receptors, whereby some cell types might be
devoid of some specific receptors while others may be enriched in a particular type of receptor.
 In some cases, receptors responsible for signal detection may form clusters on apical/basal surfaces of the
cell to produce a heightened response as observed in epidermal growth factor receptor (EGFR) signaling.

12.  Signaling Domain :-
 Signaling specificity of a protein often arises from its
domain structure. A domain is a distinctly folded part of a
protein that imparts particular functions and allows it to
differentially engage in signaling pathways.
 Proteins that are functionally alike can have distinct
domains and vice versa. Domains can be of variable length
ranging from 50–300 amino acid residues.
 Domains organize the functional units of a protein, for
example, the EF-hand domain in protein Calmodulin.
Protein domains also define the stabilizing conformations
for optimal protein folding.

13.  Transducers :-
Upon ligand binding, the receptor undergoes a conformational change and its cytoplasmic transducers or
adaptor proteins are activated depending on the type of receptor. However, the mechanistic operation of each
type of receptor varies.
Based on receptor types , signal transducers also can be categorized. In fact these signal transducers create
pathways to proper delivery of signal at responsive site.

14.  Second Messengers :-
Once the signal is relayed to the transducers, it
activates specific effectors that generate small
molecules called second messengers.
Common second messengers are cAMP, cGMP,
IP3, diacylglycerol, calcium, etc.
Cell stringently tries to maintain homeostatic
ionic fluxes within the cytoplasm by employing
active efflux pumps that pump ions back and
forth from the plasma membrane and
intracellular organelles. The ions traverse back
to form a gradient, initiating a signaling cascade.

16.  Transcription Factor :-
 The ultimate target of signaling relays are the transcription
factors that regulate gene expression and eventually allow
transforming the received signal into a change of cellular
activity.
 Some allosteric effectors can bind to regulatory
proteins (like transcription corepressors/enhancers), which
may modulate the gene expression.
 Some members of the E2F family of transcription factors
(E2F7), methyl-CpG-binding protein 2 (MeCP2), and CBF-1,
suppressor of hairless, Lag-1 (CSL) are known examples of
transcription factors that are regulated this way.

17.  Some Examples Of Cell Signal Transduction:-
 Apoptosis (Programmed Cell Death)
 Signaling For Insulin Receptor (Protein-tyrosine kinase pathway)
 Signaling At Cell Division (MAPK pathway)
 Blood Clotting Activity
Here we will be discussing about apoptosis event , like how it gets signal for it and what are all pathways are
involved in this. Apoptosis , or programmed cell death, is a normal process that is unique to animal cells.
Apoptosis occurs through an orchestrated sequence of events that leads to the death of a cell. Death by
apoptosis is a neat, orderly process characterized by the overall shrinkage in volume of the cell and its nucleus,
the loss of adhesion to neighboring cells, the formation of blebs at the cell surface, the dissection of the
chromatin into small fragments, and the rapid engulfment of the “corpse” by phagocytosis.
Apoptosis is often contrasted with a different type of cell death called necrosis, which generally follows some
type of physical trauma or biochemical insult. Like apoptosis, necrosis can also occur as a regulated and
programmed process (called necroptosis), although much less orderly in nature. Necrosis is characterized by the
swelling of both the cell and its internal membranous organelles, membrane breakdown, leakage of cell
contents into the medium, and the resulting induction of inflammation.

18. During embryonic development, T lymphocytes are produced that possess
receptors capable of binding tightly to proteins present on the surfaces of normal
cells within the body. T lymphocytes that have this dangerous capability are
eliminated by apoptosis. Apoptosis does not stop with the end of embryonic
development. It has been estimated that 10 10 –10 11 cells in the adult body
die every day by apoptosis.
For example, apoptosis is involved in the elimination of cells that have sustained
irreparable genomic damage. This is important because damage to the genetic
blueprint can result in unregulated cell division and the development of cancer.
Apoptosis is also responsible for the death of cells that are no longer required,
such as activated T cells that have responded to an infectious agent that has been
eliminated.
Finally, apoptosis appears to be involved in neurodegenerative diseases such as
Alzheimer ’ s disease, Parkinson ’ s disease, and Huntington ’ s disease.
Elimination of essential neurons during disease progression gives rise to loss of
memory or decrease in motor coordination.

19. THANK YOU