Cell signaling allows cells to communicate and respond to their environment. Extracellular signaling molecules bind to receptors on cells, which then activate intracellular responses. Prokaryotes use quorum sensing to coordinate behaviors based on population density. Eukaryotic signaling is more complex, with over 1500 receptor types in humans. Signaling pathways are classified by the signaling molecule (hormone, neurotransmitter, cytokine) and can cause changes like gene expression, enzyme activity, or cell movement. Defects in signaling can lead to diseases, making cell signaling an important area of research.
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Cell Signaling: An Introduction to its Mechanisms and Role in Health and Disease
1.
2. Introduction
Cell signalling: a biological mechanism that occurs in
cells which gives cells an ability to receive or generate
the signals in response to their surrounding
environment.
Cell to cell communication between cells is mediated
by extra-cellular signal molecules. Some of those
operate over long distances. Others signal only to
immediate neighbouring cells.
3. Definitions
Signaling - Cell-cell communication or communication of the environment to
the cells interior via signals.
Signal transduction - Process of converting extracellular signals into intra-
cellular responses.
Ligand - The signaling molecule.
Receptors - Bind specific ligands.Transmit signals to intracellular targets.
Different receptors can respond differently to the same ligand.
4. Cell signaling in prokaryotes
Korman et al. (1979) reported on the relationship
between the degree of chemotactic activity in
Escherichia coli.
They concluded: the response of the bacterial flagella
was proportional to the amount of a specific receptor
on its cell surface.
5. Long before appearance of multicellular organisms on
earth unicellular organisms had developed mechanisms
for responding to physical and chemical changes in
their environment.
Present day unicellular organisms such as bacteria and
yeast, although largely leading independent lives, they
can communicate and influence one another’s
behaviour.
Cell signaling in prokaryotes
6. Examples
1)
Many bacteria respond to chemical signals secreted by
their neighbours and increase in concentration with
increasing population density. This process called
quorum sensing.
Allows to bacteria to coordinate their behaviour
including their motility, antibiotic production, spore
formation and sexual conjugation.
Promotes survival and saves from danger
7.
8.
9. 2)
Similarly, budding yeast S. Cerevisiae communicate with one
another in preparation for mating.
A haploid individual, ready to mate, secrets a peptide called mating
factor that signals cells of the opposite mating type to stop
proliferation and prepare for mating.
10. Cell signaling in Eukaryotes
Eukaryotic signaling systems are much more elaborate
than those in yeasts or bacteria.
More than 1500 genes encode different receptor
proteins in human.
Flies, worms and mammals all use essentially similar
machinery for cell communication.
11. In plants, as in animals, cells are in constant
communication with one another.
Plant cells communicate to coordinate their activities in
response to the changing conditions of light, dark,
temperature, which guide the plants growth, flowering
and fruiting.
Plants use different signaling molecules and receptors
than animals.
Cell signaling in Eukaryotes
17. 1) Hormone-
• a class of signalling molecules produced
by glands in multicellular organisms.
• transported by the circulatory system to target distant organs to
regulate physiology and behaviour.
2) Neurotransmitter-
• endogenous chemicals that transmit signals across a synapse
from one neuron to another "target" neuron.
• released from synaptic vesicles from synapses into the synaptic
cleft, where received by receptors on other synapses.
3) Cytokines-
• signalling molecule of immune system.
19. Types of Receptors
1)G-protein coupled receptors
2)Receptor tyrosine kinase
3)Receptor guanylyl cyclases
4)Gated ion channels
5)Adhesion receptors
6)Steroid receptors
20. 1) G-protein coupled receptor-
indirectly activated through GTP binding proteins or G
proteins enzymes for example B-adregenic receptor
system that detect epinephrine.
2) Receptor tyrosine kinase-
Membrane receptors that are also enzymes,
when activated by its extracellular ligand it catalyses the
phosphorylation of several site of cytosolic domain of
receptor
Example: insulin receptor.
21. 3) Receptor guanylyl cyclases-
Membrane receptors with an enzymatic cytoplasmic domain.
intracellular second messenger e.g. cyclic guynylyl
monophosphate (cGMP) activates a cytosolic protein kinase (PK)
PK phosphorylates cellular proteins and changes their activities.
4) Gated ion channels-
Plasma membrane channel protein that open and close in response
to the binding of chemical ligands or changes in trans-membrane
potential.
Simplest signal transducers. E.g. acetylcholine receptor ion
channel
22. 5) Adhesion receptor-
Interact with macromolecule components of the ECM
such as collagen and
Conveys instructions to cytoskeleton system about cell
migration or adherence to matrix. E.g. Integrins.
6) Steroid receptors-
Bind specific ligands such as estrogen and alter the genes
transcription.
Steroid hormone function through mechanisms
intimately related to the regulation of gene expression.
23. Mechanisms of Signaling Pathway
Signal
Receptor
(sensor)
Transduction
Cascade
Output
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outside
inside (cytosol)
24.
25. Kuchh Kuchh
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Responses to cell signaling
• Gene expression altered at the level of
transcription, RNA processing or translation
• Enzyme activities are altered
• Protein-protein interactions are induced or
inhibited
• The localization of certain proteins
biochemically
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Responses to cell signaling
The Cell…
– divides or stops dividing
– differentiates
– commits suicide or kills something
– moves somewhere or stops moving
– alters its metabolism
– passes on the signal
Physiologically
28. Significance of cell signaling
Cell signaling is basis of Prokaryote and Eukaryote life
For normal functioning coordination of every signaling
pathway is necessary
Altered signaling pathways may lead to diseases
Defect can be in any component of signalling ultimately
leading to the disease development
Cell signaling has been identified in Cancer, Cardiovascular
diseases, Alzheimer's disease, and many other disorders
Cell Signaling – an important area of research for drug
discovery
30. Future of cell signalling?
With advances in separations methodology, mass
spectrometry, and hybridization, the complex protein
interactions in cellular signaling networks should
become clear.
Future cell signalling studies would involve
integration of genomic, transcriptomic, proteomic,
and metabolomic data that will provide complete
picture of cellular mechanisms and their responses.