Cell Communication

1. Cell Communication Chapter 9

2. Overview • Communication between cells requires • Ligand – signaling molecule • Receptor protein – molecule to which the receptor binds • Interaction of these two components initiates the process of signal transduction, which converts the information in the signal into a cellular response

3. Ligand-Receptor

5. LIGANDS

6. Four basic mechanisms for cellular communication • Direct contact • Synaptic signaling • Paracrine signaling • Endocrine signaling • Some cells send signals to themselves (autocrine signaling)

7. Direct Contact • Molecules on the surface of one cell are recognized by receptors on the adjacent cell • Important in early development • Gap junctions

8. Synaptic signaling • Animals • Nerve cells release the signal (neurotransmitter) which binds to receptors on nearby cells • Association of neuron and target cell is a chemical synapse

9. Paracrine signaling • Signal released from a cell has an effect on neighboring cells • Important in early development • Coordinates clusters of neighboring cells • Signaling between immune cells

10. Endocrine signaling • Hormones released from a cell travel through circulatory system to affect other cells throughout the body • Both animals and plants use this mechanism extensively

11. Signal Transduction • Events within the cell that occur in response to a signal • When a ligand binds to a receptor protein, the cell has a response • Different cell types can respond differently to the same signal • Epinephrine example (p. 170) • Glucagon example (p. 170)

12. Hormone: Epinephrine • Flight or Fight • Differing effects of epinephrine depend of the different cell types with receptors for this hormone, but different sets of proteins respond to that signal • Liver – it mobilizes glucose • Heart muscle-contract more forcefully • Blood vessels-contract or dilate

13. Hormone: Glucagon • A variety of cell respond the same way to control blood glucose • Raise blood sugar • Works on liver cells and adipose tissue • Breaks down stored glycogen into glucose by turning on the genes that make the enzymes that synthesize glucose

14. Phosphorylation • Addition of a phosphate group! • A cell’s response to a signal often involves activating or inactivating proteins • Phosphorylation is a common way to change the activity of a protein • Protein kinase – an enzyme that adds a phosphate to a protein • Phosphatase – an enzyme that removes a phosphate from a protein Don’t get confused!

16. Receptors

17. Receptor Types • Receptors can be defined by their location • Intracellular receptor – located within the cell • Cell surface receptor or membrane receptor – located on the plasma membrane to bind a ligand outside the cell • Transmembrane protein in contact with both the cytoplasm and the extracellular environment

18. Intracellular Receptors • Steroid hormones • Common nonpolar, lipid-soluble structure • Can cross the plasma membrane to a steroid receptor • Binding of the hormone to the receptor causes the complex to shift from the cytoplasm to the nucleus • Act as regulators of gene expression

20. A steroid receptor has 3 functional domains • Hormone-binding domain • DNA-binding domain • Domain that interacts with coactivators to affect level of gene transcription • In its inactive state, the receptor typically cannot bind to DNA because an inhibitor protein occupies the DNA binding site • Binding of ligand changes conformation

21. Coactivators • Target cell’s response to a lipid-soluble cell signal can vary enormously, depending on the nature of the cell • Even the same type of cell may have different responses • Depends on coactivators present • Estrogen has different effects in uterine tissue than mammary tissue • Not presence or absence of receptor but, the Presence or absence of coactivator

22. Cell Surface Receptors/ Membrane receptors • Chemically gated ion channels – channel-linked receptors that open to let a specific ion pass in response to a ligand • Enzymatic receptors – receptor is an enzyme that is activated by the ligand • Almost all are protein kinases • G protein-coupled receptor – a G-protein (bound to GTP) assists in transmitting the signal from receptor to enzyme (effector)

24. Chemically gated ion channels

25. Receptor Kinases • Protein kinasesphosphorylate proteins to alter protein function • Receptor tyrosine kinases (RTK) • Influence cell cycle, cell migration, cell metabolism, and cell proliferation • Alteration to function can lead to cancer • Membrane receptor • Plants possess receptors with a similar overall structure and function

28. Insulin receptor (… how RTK works to lower blood sugar) • Insulin is a hormone that helps to maintain a constant blood glucose level • Glucose is bonded with other glucose molecules and converted to a glycogen molecule • Lowers blood glucose

29. Summary of RTKs • A single transmembrane domain • Anchors them in membrane • Extracellular ligand-binding domain • Intracellular kinase domain • Catalytic site of receptor acts as protein kinase • Process: • When a ligand bind: • dimerization and autophosphorylation occurs • Cellular response follows – depends on cellular response proteins

30. G-Protein Coupled Receptors • G Proteins are transmembrane receptors • Single largest category of receptor type in animal cells is GPCRs

31. G-Protein Coupled Receptors • Sense molecules on OUTSIDE of cell (ligand) • Hormones, light sensitive compounds, neurotranmsitters, pheromones, odors • Activate a signal transduction INSIDE of the cell– ultimately leading to a response. • Open a gated channel • Enzymatic reaction

32. http://www.youtube.com/watch?v=NB7YfAvez3o G-Protein

34. Smell you later…

35. Often, the effector proteins activated by G proteins produce a second messenger 2 common effectors • Adenylyl cyclase • Produces cAMP (helpful for hormones that cannot get through cell membrane) • cAMP binds to and activates the enzyme protein kinase A (PKA) • PKA adds phosphates to specific proteins • Phospholipase C • PIP2 is acted on by effector protein phospholipase C • Produces IP3 plus DAG • Both act as second messengers

37. http://www.rci.rutgers.edu/~uzwiak/AnatPhys/ChemicalSomaticSenses.htmhttp://www.rci.rutgers.edu/~uzwiak/AnatPhys/ChemicalSomaticSenses.htm

38. Different Signals, Same Effect • Different receptors can produce the same second messengers • Hormones glucagon and epinephrine can both stimulate liver cells to mobilize glucose • Different signals, same effect • Both act by same signal transduction pathway

40. Single signaling molecule can have different effects in different cells • Existence of multiple forms of the same receptor (subtypes or isoforms) • Receptor for epinephrine has 9 isoforms • Encoded by different genes • Sequences are similar but differ in their cytoplasmic domains • Different isoforms activate different G proteins leading to different signal transduction pathways