Cell Communication dnalc/ddnalc/cell_signals/index.html

1. Cell Communicationhttp://www.dnalc.org/ddnalc/cell_signals/index.html

2. Cell Signaling • Signal-transduction pathway- how a signal on a cell’s surface is changed into a cellular response. • Cells secrete local regulators which is a substance that influences cells that are near. Ex. Growth factors, compounds that trigger cells to grow and multiply • A common compound used in animals and plants are hormones.

3. Cell Signaling Cont.. • Two types of information available • 1. Direct physical aspects of the environment • 2. Symbolic information encoded by other cells

4. Overview of Cell signaling http://www.dnatube.com/video/233/The-Signal-Transduction-Pathway

5. Symbolic information is required for multicellular organisms • Bacteria (unicellular organisms) sense their environment and change their behavior (i.e. chemotaxis). • To coordinate the behavior of populations of cells, cells in multicellular organisms must exchange data. • http://www.sysbio.org/resources/tutorials/2003series/biolecture5.pdf

6. Vocabulary • Hormone -circulating, global regulator made by endocrine glands http://www.sumanasinc.com/webcontent/animations/content/extracellularsignaling.html • Growth factor -polypeptide that promotes cell growth and/or proliferation • Cytokine -general term for a growth factor, derived from immunology • Chemokine -small factor involved in cell attraction and migration

7. Examples of Cell Signaling http://www.dnatube.com/video/2349/Synaptic-Signaling http://www.allthingsscience.com/video/665/The-Endocrine-System-How-it-Works

8. Communication by Direct Contact Between Cells

9. Interaction of Cell-Surface Molecules

10. Stages of Cell Signal • 1. Reception- a chemical signal is detected when it binds to a cellular protein, usually at the cells surface. • A cell needs to communicate with its environment so that it can make appropriate responses. The external signal may enter a cell via four major pathways: • 1.Hydrophobic molecules. http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__intracellular_receptor_model.html • 2.Ion channels. • 3.G-protein-coupled receptors. • 4.Enzymes.

11. Enzymes G-protein-coupled receptors Hydrophobic molecules. Ion channel

12. Stages of Cell Signal Cont.. • 2. Transduction-The binding of the signal molecule changes the receptor protein in some way, in order to initiate the process of transduction. This stage converts the signal to a form that can bring about a specific cellular response. Transduction often occurs in a single step but more often requires a sequence of changes in a series of different molecules- a signal-transduction pathway. The molecules in the pathway are often called relay molecules.

13. Transduction

14. 3. Response- the transduction triggers a response. http://cgmp.blauplanet.com/transd.html Stages of Cell Signal Cont.. Reception Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Active protein kinase A (105) Inactive protein kinase A Active phosphorylation Inactive phosphorylase kinase Inactive glycogen phosphorylase Active glycogen phosphorylase (106)) Response Glycogen Glucose-1-phosphate (108 molecules)

15. Ligand • A signal molecule binds to a receptor protein, causing the protein to change shape. • A ligand is a small molecule that binds to a larger one. • Ligand binding generally causes a receptor protein to undergo a change in shape. For many receptors this change directly activates the receptor so that it can interact with another cellular model.

16. Plasma-Membrane proteins • 1. G-protein-linked receptors- is a plasma-membrane receptor that works with the help of a protein called G protein linked receptors, including epinephrine and other hormones and neurotransmitters. All G protein receptor molecules are structurally similar. The G protein functions as a switch that is on or off depending on which guanine nucleotides is attached, GDP or GT When GDP is bound it is inactive, when GTP is bound it is active. (GTP or guanosine triphosphate is similar to ATP). • When the appropriate chemical signal binds as a ligand to the outside of a G-protein-linked receptor, the receptor is turned on changing the conformation in a way that it, in turn can activate a G protein.

18. G Protein Cont… • The receptor binds a specific, inactive G protein and causes a GTP to displace the GDP. The activated G protein then binds to another protein, usually an enzyme and alters its activity. • This is temporary for the G protein also functions as a GTPase enzyme. The GTPase function of the G protein allows the pathway to shut down rapidly when the outside signal is no longer present. • http://www.celanphy.science.ru.nl/Bruce%20web/Flash%20Movies.htm

19. Cont.. • G proteins are involved in sensory reception. Ex: vision (vitamin A) and smell. • 60% of all medications used today are a result of an influence on a G protein pathway. • http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__membrane-bound_receptors_that_activate_g_proteins.html • http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__membrane-bound_receptors__g_proteins__and_ca2__channels.html

20. Plasma-Membrane proteins Cont… • 2. Tyrosine-Kinase Receptors- tyrosine kinase an enzyme, catalyzes the transfer of phosphate groups from ATP to the amino acid tyrosine on a substrate protein. The tyrosine-kinase receptors are the membrane receptors that attach phosphates to protein tyrosines. • http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&B

21. Tyrosine Cont.. • A. The ligand binding causes two receptor polypeptides to come together, making a dimer (a protein consisting of 2 polypeptides). • B. This activates the tyrosine-kinase of both • C. Which phosphorylates the tyrosines on the tail of the other • http://faculty.plattsburgh.edu/donald.slish/tyrosinekinase/TK1.html • Abnormal tyrosine-kinase that come together without ligand can cause cancer.

22. Plasma-Membrane proteins Cont… • 3. Ion-Channel Receptors • These are ligand gated ion channels that are protein pores in the plasma membrane that open or close in response to a chemical signal, allowing or blocking the flow or specific ions such as Na+ or Ca2+. • These channel proteins bind a signal molecule as a ligand at a specific site on the outside of the cell. The shape change produced in the channel protein immediately leads to a change in the concentration of a particular ion in the cell. • Ex: Synapse between nerve cells

23. Ion-Channel Receptors • http://www.mind.ilstu.edu/flash/synapse_1.swf • http://www.wiley.com/legacy/college/boyer/0470003790/animations/membrane_transport/membrane_transport.htm

24. Intracellular receptors • Some signal receptors are proteins located in the cytoplasm or nucleus of target cells. So in order to reach the receptor a chemical message must be able to pass through the target cells membrane. • Ex: Testosterone, it enters the target cells binds to the receptor molecules, activating it. The protein then can bind and turn on genes in the nucleus that control male sex characteristics.

25. Intracellular Animation • http://highered.mcgraw-hill.com/olc/dl/120069/bio06.swf

26. Advantages • A very small number of extracellular signal molecules can produce a major cellular response. • Multistep pathways provide more opportunities for coordination and regulation than simpler systems. • To Amplify the signal: • http://highered.mcgraw-hill.com/olc/dl/120069/bio08.swf

27. Protein Phosphorylation • Phosphorylation is a common mode of cell regulation. • Protein kinase is the name for an enzyme that transfers phosphate groups from ATP to a protein. • Most cytoplasmic protein kinases act on other substrate proteins and phosphorylate their substrates on either the amino acid serine or threonine. • These are common in animals, fungi and plants. • http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&C

28. Phosphorylation Cascade

29. Second Messengers • Many signaling pathways involve small, nonprotein, water-soluble molecules or ions call second messengers. • The extracellular signal molecule that binds to the membrane receptor is the first messenger.The second messenger is small and water-soluble so can pass through the membrane by diffusion.That relay the message from the inside of the membrane throughout the cytoplasm. • Ex: cAMP (cyclic AMP) that carries the signal initiated by epinephrine from the plasma membrane of a liver or muscle cell into the cell’s interior

30. cAMP • cAMP (cyclic AMP (adenine monophosphate) ). • An enzyme built into the cell membrane, adenylyl cyclase, converts ATP to cAMP in response to an extracellular signal, in this case epinephrine. Adenylyl cyclase only becomes active only after epinephrine binds to a specific receptor protein. • So the first messenger the hormone, causes a membrane enzyme to make cAMP, which sends the signal to the cytoplasm.Then another enzyme converts the cAMP into an inactive form. In order for this to happen again you need more epinephrine.

31. cAMP • http://highered.mcgraw-hill.com/olc/dl/120069/bio07.swf

32. Disease • Some diseases, like cholera produce an enzyme that changes a G protein that is involved in regulating salt and water secretion. Because the changed protein can no longer hydrolyze GTP to GDP, it remains stuck in its active form, continuing to stimulate cAMP causing intestinal cells to secrete large amounts of water and salts into the intestine. Which results in bad diarrhea and the victim can die if untreated.

33. Calcium • Another second messenger is Ca+ in G pathways and tyrosine-kinase receptor pathways. • Ca+ that is released from the ER triggers cleavage of certain phospholipids on the cell membrane.

34. Cellular Responses • These can result in activities in the cytoplasm such as a rearrangement of the cytoskeleton. • Sometimes they regulate the making enzymes or other proteins by turning off or on specific genes. • Cellular responses are very specific. Different kinds of cells have different collections of proteins. • One signal molecule may lead to more than one response, activate or inhibit another response. • http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&D

35. Activity • http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&E