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Introduction of cell signaling

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cell signaling mechanism

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Introduction of cell signaling

  1. 1. 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.
  2. 2. 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.
  3. 3. 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.
  4. 4.  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
  5. 5. 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
  6. 6. 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.
  7. 7. 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.
  8. 8.  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
  9. 9. Properties of cell signaling Specificity Affinity Cooperativity Sensitization Amplification Integration
  10. 10. Classification of signaling pathway Autocrine Paracrine Endocrine Juxtracrine Synaptic
  11. 11. Classification of signaling pathway
  12. 12. Cell signaling components Signalling molecule Receptor Signalling intermediate Effector proteins
  13. 13. Types of signalling molecules 1) Hormone 2) Neurotransmitter 3) cytokines
  14. 14. 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.
  15. 15. Chemical classes 1)Amino acid 2)Lipid 3)Phospholipid 4)Monoamines 5)Proteins 6)Glycolipid
  16. 16. 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
  17. 17.  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.
  18. 18.  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
  19. 19.  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.
  20. 20. Mechanisms of Signaling Pathway Signal Receptor (sensor) Transduction Cascade Output Kuchh Kuchh hota hai outside inside (cytosol)
  21. 21. Kuchh Kuchh hota hai 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
  22. 22. Kuchh Kuchh hota hai 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
  23. 23. Extracellular signals can act slowly or rapidly to change the behavior of a target cell
  24. 24. 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
  25. 25. Diseases and cell signaling • Cancer • Alzheimer’s disease • Diabetes • Epilepsy • Heart disease • Hypertension • Metabolic syndrome
  26. 26. 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.
  27. 27. References • The cell- Albert • Cell – Lewis • Biochemistry- Lehninger

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