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Cell signalling

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signal transduction in the cell and between the cell.

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Cell signalling

  1. 1. INTRACELLULAR SIGNALLING AND EXTRACELLULAR SIGNALLING Prepared by: Sindhoora D First M pharm. Department of Pharmacology SCP,Manglore 1
  2. 2. CONTENTS: • Introduction to cell signalling • Signal transduction • Types of signalling pathway Extracellular signalling Intracellular signalling 2
  3. 3. CELL SIGNALLING: Cell signalling is a type of any communication process that governs the basic activities of cell and coordinate all cell action. Interact with the cellular environment and neighbouring. This involves determining function of the cell within context of the organism as well as the response of specific cells or group of cell to the environment. Communicate using chemical signals. 3
  4. 4. These chemical signals, which are protein or other molecules produced by a sending cell are often secreted from the cell and released into extracellular space. Float like a messenger in a bottle over to neighbouring cell. When binds to the receptor, it alters the shape or activity of the receptor, triggering a change inside the cell. They are often ligands. Causes the chain of chemical messenger inside the cell. 4
  5. 5. Ultimately ,causes change in the activity of cell. The extracellular signalling is convert to intracellular signalling. Importance of signals: • Maintenance of homeostasis. • Control of cell division and cell death &development and growth. • Adaptation to environment. • Hormones and other regulatory mediators. • Establishment of pathogenesis &symbiosis,activation of defences. 5
  6. 6. Signal transduction: It is a process by which cell receive, propagate and respond to information from their environment and each other. Transmision across the membrane,converting extracellular to intracellular signals. Some cases ,additional protein and small molecule participate in relaying the message to its ultimate destination in the cell where a response is evoked. 6
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  8. 8. Steps:  Biosynthesis and release of the signal.  Transport of signals to target cell  Transduction in target cell.  Alteration of cell growth and metabolism.  Termination of signals 8
  9. 9. 16_08_cascades.jpg 9
  10. 10. Types of signalling pathway: • Extracellular signalling: Signalling occurs between the cells ,it may be a neighbouring cell or a cell in other part of body. There are 4 types of signalings: Contact dependent Paracrine Synaptic endocrine 10
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  12. 12. Contact dependent : • Bound to the surface of the signalling cells and influence only cells that contact it. • The cell makes direct physical contact with a target cell with the plasma membrane of the protein. • Immune response • Short distance • Sometimes through a gap junction 12
  13. 13. Paracrine : • Signalling molecules released from the signalling cell to the extracellular space ,targeting cells that nearby ,thus acting as a local mediator . • Inflammation during infection ,regulate cell proliferation • They act on the cell in the local environment or in the receptors of own cell it is known as autocrine signalling • Cancer cell often produce extracellular signals that stimulates their own survival and proliferation 13
  14. 14. Synaptic : • the synaptic space.These neurotransmitter are detected by receptors on the postsynaptic membrane i.e cell meVery quick, long distance and specific to target cell • A signal is detected by receptors present on dendrites and then carried along the axon to a presynaptic terminal.When the signal reaches the presynaptic terminal,vesicles containing signalling molecules (neurotransmitter) fuse with the membrane,releasing the content into mbrane of target cell,which may be another neuron or an effector cell. • Ex:Ach,serotonin,histamine. 14
  15. 15. Endocrine: • distance,signall molecules are harmones • Blood carries the molecule far and wide,allowing them to act on target cells that may lie in the body. • Ex:pancrease secrete insulin,progesterone, testosterone 15
  16. 16. Types of receptors: 1. Cell surface receptor  unable cross the cell membrane , instead they bind to cell surface receptor.  Cell surface receptor are also called cell specific protein or markers because they are specific to individual cell type. 16
  17. 17. 2.Intracellular receptor: • Molecules are hydrophobic, poorly aqueous soluble.Therefore they are transported in the bloodstream and extracellular fluid bound to carrier protien , from which they are dissociated before entering the target cell. • Binds to the receptor protein in the cytosol or in the nucleus. • Ex:mRNA synthesis in the gene expression 17
  18. 18. Cell is programmed to respond to specific signals: • Cell integrates all this signals to make decision –to devide, move,differentiate,.Cell requires a specific combination of extracellular survival factor to allow the cells to continue living,when deprived of these signals,the cell undergoes apaptosis. • Cell proliferation often depends on the combination of signals that promote both cell division and survival. • Differention into non dividing state frequently requires a different combination of survival &differention signals that must override any signal to divide. 18
  19. 19. 16_06_extracellular_sig.jpg 19
  20. 20. • A signal molecules has different effects on different target cell. • Ex:Ach decreases the action potential firing in heart pacemaker cell and stimulates the production of saliva by salivary gland cell even tough receptor are same on the both the cells. • In skeleton muscles, Ach causes cell to contract by binding to a different receptor protein • Difference in the intracellular signalling protein,effector protein and gene that are activated. 20
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  22. 22. •Intracellular signalling: • Activation of receptors can trigger the synthesis of small molecules called second messengers , which initiate and coordinates intracellular signalling pathway.ex:cAMP • Generates the second messenger or activating the next signalling or effector protein in the pathway. Behave like a molecular switches. • When they receive a signals ,they switch from an inactive to an active state, untill another process switches them off and recovering after transmitting a signal 22
  23. 23. • Molecular switches consists of protein that are activated or inactivated by phosphorylation .For these proteins, the switch is thrown in one direction by a protein kinase,which is covalently adds one or more phosphates groups to specific amino acids on the signalling proteins,in other direction by a protein phosphate ,which removes phosphate group.It depends on the balance between the activities kinase that phosphorylate it and of the phosphates that dephosphorylate it. 23
  24. 24. • Protein kinase attach phosphate to the –OH group of the amino acids in the target protein. • Two types –serinethreonine kinase,tyrosine kinase • This is known as kinase cascades. 24
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  26. 26. • GTP-binding protien switch between an ”on” state when GTP is bound and an “off” state when GDP is bound. • On state they have intrinsic GTPase activity and shut themselves off by hydrolysing their bound to GTP to GDP. • Large Trimeric GTP binding protein help relay signals from G-protein –coupled receptor that activate them • Small monomeric GTPase help relay signals from many classes of cell surface receptor 26
  27. 27. Three major class of cell surface receptor : 1. Ion channel coupled receptor: • Involved in rapid synaptic signalling between nerve cells and other electrically excitable target cells such as nerve and muscle cells. • Mediated by small no.of neurotransmitter that transiently open or close an ion channel formed by the protein to which they bind ,briefly changing the ion permeability of the plasma membrane and thereby changing the excitability of the postsynaptic target cells 27
  28. 28. 2.G-protein coupled receptor:  Indirectly regulating the activity of a separate plasma membrane bound target protein,which is generally enzyme or ion channel.  Trimeric GTP binding protein mediates  Change the concentration of one or more small molecules(enzyme),change the ion permeability(ion) 28
  29. 29. 3.Enzyme coupled receptors: • Function as a enzyme or associates directly with enzyme that they activate. • They have ligand binding site outside the cell and their catalytic or enzyme binding site inside. • Heterogeneous in structure compared with other • Protein kinase or associated with protein kinase 29
  30. 30. 16_18_Gprot_subunit.jpg 30
  31. 31. Some regulate ion channels 31
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  33. 33. Reference 1. Molecular cell biology, seventh edition, Lodish ,berk kaiser,amon 2. Molecular biology of THE CELL ,sixth edition ,Bruse albert,Alexander Johnson ,Julian Lewis 3. The cell a molecular approach ,Fifth edition,Geoffrey M.Cooper,Robert E.Hausman 4. www.slide share .com 33