Cell Communication

1. Cell Communication

2. The Cellular “Internet” • Within multicellular organisms, cells must communicate with one another to coordinate their activities • A signal transduction pathwayis a series of steps by which a signal on a cell’s surface is converted into a specific cellular response • Signal transduction pathways are very similar in all organisms, even organisms as different as unicellular yeasts and multicellular mammals

3. Local (Short-Distance) Signaling • Cells may communicate by direct contact • Plasmodesmata in plant cells • Gap junctions in animal cells • Animal cells can also use cell-cell recognition • Membrane-bound surface molecules can interact and communicate

4. Local (Short-Distance) Signaling • Messenger molecules can also be secreted by the signaling cell • Paracrine signaling: • One cell secretes (releases) molecules that act on nearby “target” cells • Example: growth factors • Synaptic Signaling: • Nerve cells release chemical messengers (neurotransmitters) that stimulate the target cell

5. Long-Distance Signaling • Endocrine (hormone) signaling • Specialized cells release hormone molecules, which travel (usually by diffusion through cells or through the circulatory system) to target cells elsewhere in the organism

6. The Three Stages of Cell Signaling • There are 3 stages at the “receiving end” of a cellular conversation: • Reception • Transduction • Response

7. Stage 1: Reception • The target cell “detects” that there is a signal molecule coming from outside the cell • The signal is detected when it binds to a protein on the cell’s surface or inside the cell (receptor protein) • The signal molecule “searches out” specific receptor proteins • The signal molecule is a ligand • It is a molecule that specifically binds to another one and induces a change in the shape of the receptor protein • Ligands can be hydrophobic or hydrophillic

8. Receptor proteins • There are 2 different types of receptor proteins: • Membrane receptors: transmembrane proteins • Intracellular receptors: proteins that occur in the cytoplasm or the nucleus

9. Second messengers • Molecules that relay messages from membrane receptors to other molecules • They are all: • Small, nonprotein molecules • Either hydrophillic, hydrophobic, or gaseous • Ex. Ca ions, IP3, CAMP, and DAG

10. Stage 2: Transduction • This stage converts the signal into a form that can bring about a specific cellular response • One signal-activated receptor activates another protein, which activates another molecule, etc., etc. - this is called a signaling cascade • These act as relay molecules • Often the message is transferred using protein kinases, which transfer phosphate groups from ATP molecules to proteins • These can be very complicated

11. Stage 2: Transduction

12. Advantages of signal transduction • Amplification: the effect of the signaling molecule can be amplified • Control: the cell can control the accuracy of the signaling • Multiplicity: a signaling molecule can start many different processes at once to respond to the signal

13. Stage 3: Response • The signal that was passed through the signal transduction pathway triggers a specific cellular response • Examples: enzyme action, cytoskeleton rearrangement, activation of genes, etc., etc. • Diagram example: transcription of mRNA

14. The Specificity of Cell Signaling • The particular proteins that a cell possesses determine which signal molecules it will respond to and how it will respond to them • Liver cells and heart cells, for example, do not respond in the same way to epinephrine because they have different collections of proteins

15. Receptors and their responses

17. Receptors and their responses

19. Receptors and their responses

21. Receptors and their responses

22. When cell signaling doesn’t work • Signal transduction pathways can be blocked or defective • Examples: • Diabetes • Cholera • Autoimmune disease • Cancer • Neurotoxins, poisons, pesticides • Drugs (anesthetics, antihistamines, blood pressure meds)

23. Cholera • Disease acquired by drinking contaminated water (w/human feces) • Bacteria (Vibrio cholerae) colonizes lining of small intestine and produces toxin • Toxin modifies G-protein involved in regulating salt & water secretion • G protein stuck in active form  intestinal cells secrete salts, water • Infected person develops profuse diarrhea and could die from loss of water and salts

24. Apoptosis = cell suicide • Cell is dismantled and digested • Triggered by signals that activate cascade of “suicide” proteins (caspase) • Why? • Protect neighboring cells from damage • Animal development & maintenance • May be involved in some diseases (Parkinson’s, Alzheimer’s) • Interference may contribute to cancers

25. Apoptosis of a human white blood cell Left: Normal WBC Right: WBC undergoing apoptosis – shrinking and forming lobes (“blebs”)

26. Effect of apoptosis during paw development in the mouse

27. Drugs • There are drugs that interfere with cell signaling • can either be agonists or antagonists • Agonists: acts the same way that a ligand does • Antagonists: blocks the binding site of the receptor and does not let cell signaling occur • Ex. The poison curare blocks the binding sites for the chemical acetylcholine which will cause muscle paralysis and death