Cell Communication

1. Cell Communication Signaling molecules & Cell surface receptors

2. Cell Communication

3. Cell Communication: An Overview • Cells communicate with one another through • Direct channels of communication • Specific contact between cells • Intercellular chemical messengers

4. Receptor animation • Cell surface receptors

5. Cell Communication • To survive, cells must • Communicate with their neighbors • Monitor environmental conditions • Respond appropriately

6. Cell Signaling

7. Apoptosis Fig. 7-1, p. 140

8. Signals relayed between cells • Direct intercellular signaling • Cell junctions allow signaling molecules to pass from one cell to another • Contact-dependent signaling • Some molecules are bound to the surface of cells and serve as signals to cell coming in contact with them • Autocrine signaling • Cells secrete signaling molecules that bind to their own cell surface or neighboring cells of the same type

9. Signals relayed between cells • Paracrine signaling • Signal does not affect cell secreting the signal but does influence cells in close proximity (synaptic signaling) • Endocrine signaling • Signals (hormones) travel long distances and are usually longer lasting

11. Cell Signaling

14. Signaling Molecules • Small molecules • Peptides • Proteins • LIGANDS

15. Receptor affinity • High affinity • Low concentration of ligand; most receptors are occupied • Low affinity • High concentration of ligand for most rectors to be occupied

16. Receptor affinity • Dissociation constant Kd • Measures the affinity of the receptor-ligand complex • The concentration of ligand at which half the receptors are occupied

18. Example • Erythroid progenitor cell ~1000 surface receptors for erythropoietin (Epo) • Only 100 receptors need to bind Epo to induce cell division • Max cellular response less than Kd

19. Vasoconstriction occurs when epinephrine (adrenaline) binds to the a-adrenergic receptor on vascular smooth muscle cells. One approach to treating high blood pressures is to administer competitive inhibitors that bind to the a-adrenergic receptor. The Kd for binding of epinephrine to this receptor is ~0.6 mM. Which of the following compounds might be good candidate drugs for high blood pressure? Kd for binding to the a-adrenergic receptor are shown. • Compound A: Kd = 1pM • Compound B: Kd = 0.6 mM • Compound C: Kd = 60 mM

20. Intercellular Chemical Messengers • Controlling cell • Releases signal molecule that causes response of target cells • Target cellprocesses signal in 3 steps: • Reception, transduction, response • Signal transduction • Series of events from reception to response

21. 3 stages of cell signaling • Receptor activation • Signaling molecule binds to receptor • Signal transduction • Activated receptor stimulates sequence of changes- signal transduction pathway • Cellular response • Several different responses • Alter activity of 1 or more enzymes • Alter structural protein function • Change gene expression– transcription factor

22. Signal Transduction Fig. 7-2, p. 142

24. Amazing cells • animation

25. Which of the following best describes a signal transduction pathway? • Binding of a signal molecule to a cell protein • Catalysis mediated by an enzyme • Series of changes in a series of molecules resulting in a response

26. a. Reception by a cell-surface receptor Polar (hydrophilic) signal molecule Receptor embedded in plasma membrane Activation Target cell Plasma membrane Polar signal molecules cannot pass through the plasma membrane. In this case they bind to a receptor on the surface. Fig. 7-3a, p. 142

27. b. Reception by a receptor within cell Nonpolar (hydrophobic) signal molecule Activation Receptor within cell Nonpolar signal molecules pass through the plasma membrane and bind to their receptors in the cell. Fig. 7-3b, p. 142

28. Intracellular receptors • Some receptors are inside the cell • Estrogen example • Passes through membrane and binds to receptor in nucleus • Dimer of estrogen•receptor complexes binds to DNA • Transcription factors regulate transcription of specific genes

30. Cell Communication Systems with Surface Receptors • Peptide hormonesandneurotransmitters • Primary extracellular signal molecules recognized by surface receptors in animals • Surface receptors • Integral membrane glycoproteins • Signaling molecule • Bound by a surface receptor • Triggers response pathways within the cell

31. Surface Receptors • Cell communication systems based onsurface receptorshave 3 components: (1) Extracellular signal molecules (2) Surface receptors that receive signals (3) Internal response pathways triggered when receptors bind a signal

32. Peptide Hormones • Peptide hormones • Small proteins • Growth factors • Special class of peptide hormones • Affect cell growth, division, differentiation

33. Neurotransmitters • Neurotransmittersinclude • Small peptides • Individual amino acids or their derivatives • Chemical substances

34. Surface Receptors • Surface receptors • Integral membrane proteins • Extend entirely through the plasma membrane • Binding of a signal molecule • Induces molecular change in the receptor that activates its cytoplasmic end

35. Ligand • Signaling molecule • Binds noncovalently to receptor with high degree of specificity • Binding and release between receptor and ligand relatively rapid • Ligands alter receptor structure- conformational change • Once a ligand is released, the receptor is no longer activated

36. Response of Surface Receptor Fig. 7-4, p. 143

38. Cellular Response Pathways • Cellular response pathways • Operate by activatingprotein kinases • Protein kinasesadd phosphate groups • Stimulate or inhibit activities of target proteins, producing cellular response

40. Cellular Response Pathways • Protein phosphatases • Reverse response • Remove phosphate groups from target proteins • Receptors are removed by endocytosis • When signal transduction is finished

41. Phosphorylation Fig. 7-5, p. 144

42. Amplification • Each step of a response pathway catalyzed by an enzyme is amplified • Each enzyme activates hundreds or thousands of proteins that enter next step in pathway • Amplification • Allows full cellular response when few signal molecules bind to receptors

43. Amplification Fig. 7-6, p. 145

46. Which of the following steps in an intracellular signaling pathway amplifies the signal? • Synthesis of a secondary messenger • Activation of a protein kinase • Binding of ligand to receptor • 1 & 2

47. In reactions mediated by protein kinases, what does phosphorylation of successive proteins do to drive the reaction? • Make functional ATP • Change a protein from its inactive to active form • Change a protein from its active to inactive form

48. Which of the following is an example of signal amplification? • catalysis of many cAMP molecules by several simultaneously binding signal molecules • activation of 100 molecules by a single signal binding event • activation of a specific gene by a growth factor

49. Cell surface receptors • Enzyme-linked receptors • Found in all living species • Extracellular domain binds signal • Causes intracellular domain to become functional catalyst • Most are protein kinases

50. Receptor Tyrosine Kinases • Receptor tyrosine kinasesbind signal molecule • Protein kinase site becomes active • Adds phosphate groups to tyrosines in the receptor itself, and to target proteins • Phosphate groups added to cytoplasmic end of receptor are recognition sites for proteins activated by binding to the receptor