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  1. CELL COMMUNICATION Campbell & reece Chapter 11

  2. Cell Messaging some universal mechanisms of cellular regulation cells most often communicate with other cells by chemical signals

  3. Evolution of Cell Signaling Yeast: Saccharomycescerevisia 2 sexes: a & α type a secrete a signaling molecule called “a factor” which can bind to receptor proteins on α cells @ same time α cells secrete “α factor” which binds to receptor proteins on type a cells

  4. Saccharomycescerevisiae 2 mating factors then cause the 2 yeast cells to grow toward each other & initiate other cell changes results in fusion or mating of 2 cells of opposite type  a/α cell that contains genes of both original cells this new cell later divides passing this genetic combination to their offspring

  5. Signal Transduction Pathway series of steps initiated by signal molecule attaching to receptor mechanism similar in yeasts and mammals & between bacteria and plants Scientists think signaling mechanisms 1st evolved in ancient prokaryotes & unicellular eukaryotes then adopted for new uses by their multicellular descendants

  6. Communication Among Bacteria quorum sensing: bacteria release small molecules detected by like bacteria: gives them a “sense” of local density of cells allows them to coordinate activities only productive when performed by given # in synchrony ex: forming a biofilm: aggregation of bacteria adhered to a surface: slime on fallen leaves or on your teeth in the morning (they cause cavities)

  7. BiofilmDeveloping

  8. Biofilm Development

  9. Local Signaling (eukaryotic cells can also use cell junctions) secretion of chemicals = messenger molecules from signaling cell messenger molecules that travel to nearby cells only called: local regulators

  10. Local Regulators Animals: use 1 class of local regulators: growth factors many cells in neighborhood respond to growth factor produced by 1 cell paracrine signaling: secreting cell acts on nearby target cells by discharging local regulator

  11. Paracrine Signaling

  12. Synaptic Signaling in the animal nervous system action potential travels thru cell membrane of neuron  when the electrical signal reaches axon end it triggers exocytosis of neurotransmitter (messenger molecule) neurotransmitter travels across small space (synapse)  attaches to receptors on target cell

  13. Synaptic Signaling

  14. Local Signaling in Plants • not as well understood as in animals • use hormones (as do animals): long distance signaling aka endocrine signaling • travel  target cells (any cell that has receptor for hormone) • Plant hormones aka plant growth regulators • most reach their targets by moving cell-to-cell • some travel in vessels

  15. Long Distance Signaling hormones (in some cases) neurotransmitters: electrical signal travels length of neuron, may go from neuron-to-neuron for long distances ability for any cell to respond to messenger molecule requires cell to have receptor for that particular molecule

  16. 3 Stages of Cell Signaling • Reception • target cell’s detection of the signal • Transduction • receptor protein changes converting signal to a form that can bring about specific cellular response via a signal transduction pathway • Response • activation of cellular response

  17. Stages of Cell Signaling Response

  18. Reception • cells must have a receptor for the ligand (messenger molecule) to react with • many signal receptors are transmembrane proteins with water-soluble ligands ligands: usually large hydrophilic

  19. Membrane Receptors

  20. G-Protein-Coupled Receptors • cell-surface transmembrane receptor • works with help of a G protein (protein that binds to GTP) • flexible • inherently unstable • difficult to crystallize so can study structure (use x-ray crystallography)

  21. G Protein-Coupled Receptor: 7 α helices

  22. Receptor Tyrosine Kinases major class of membrane receptors w/enzyme activity kinase: enzyme that catalyzes addition of phosphate group cytoplasmic side of receptor has enzyme that: phosphate group from ATP  tyrosine (on substrate protein)

  23. Tyrosine

  24. Inactive Monomers of Tyrosine Kinase When there is no ligand attached to receptor site the kinase receptor protein exists as monomers

  25. Binding of Signaling Molecule: Form Dimers

  26. Tyrosine Kinase Activated by Dimerization phosphate group added to each tyrosine

  27. Recognition by Relay Proteins Relay proteins attach to phosphorylated tyrosine  structural change that activates the bound protein Each activated relay protein triggers different transduction pathway  specific cellular response

  28. ION CHANNEL RECEPTORS Ligand-Gated Ion Channels

  29. Ligand Binds to Receptor Site ion crosses membrane & enters cytoplasm  transduction pathway leading to a response

  30. Ligand Dissociates from Receptor Site

  31. Intracellular Receptors in cytoplasm or nucleus of target cells hydrophobic or very small ligands examples steroid hormones & thyroid hormones of animals NO (nitric oxide), a gas

  32. Turning on Genes • special proteins called transcription factors control which genes are turned on • example: • Testosterone (steroid hormone) • its activated receptor acts as transcription factor that turns on specific genes • thus activated receptor carries out transduction of the signal

  33. TRANSDUCTION • when receptors for signaling molecules are membrane proteins the transduction stage is multistep pathway • usually involves inactive/active state by adding/removing phosphate group • benefit of multistep pathway is that possibility of amplification of signal • if each step on pathway can transmit signal to several molecules end up with large # activated molecules @ end of pathway

  34. Signal Transduction Pathway in most cases original signaling molecule does not enter cell & is not passed along signaling pathway 1st step triggered by signaling molecule binding to receptor proteins often used as relay molecules (protein interaction a unifying theme of all cellular regulation)

  35. Protein Phosphorylation & Dephosphorylation • protein kinase: enzyme that transfers phosphate groups from ATP  protein • most act on proteins different than themselves • most act on a.a. serine or threonine (not tyrosine as in previous example) • includes kinases in plants, animals, & fungi • many relay molecules in pathway are kinases

  36. Phosphorylation Cascade

  37. Protein Phosphatases enzymes that can rapidly remove phosphate groups from proteins (inactivating them) also make kinases available to reuse this phosphorylation/dephosphorylation system acts as molecular “switch” in cell “position of the switch” @ any given time depends on balance between active kinase & active phosphatase molecules

  38. Second Messengers many signaling pathways involve small, nonprotein, water-soluble molecules or ions known as 2nd messengers 1st messenger is extracellular signaling molecule 2 most widely used 2nd messengers are cAMP & Ca++

  39. Cyclic AMP epinephrine causes glycogen in hepatocytes to  glucose w/out entering cells search for 2nd messenger that transmits signal from plasma membrane  metabolic pathway in cytoplasm epinephrine binding to receptor followed by elevation of cytosolic concentrations of cAMP

  40. cAMP

  41. ATP cAMP

  42. AdenylylCyclase enzyme embedded in plasma membrane ATP  cAMP in response to extracellular signals directly or indirectly(epinephrine one of many) indirectly: receptor protein changes when signaling molecule attaches  activates many adenylylcyclase possibly thru GTP