Signaling & Communication in Cells

1. Signaling & Communication in Cells

2. Basic Key Vocabulary homeostasis: organisms maintain a stable level or condition at the cellular and whole-organism level receptor: site on cell that is activated by a stimulus; presence of stimulus alone is not enough for a response; receptor must match the signal signal/stimulus: hormones, population size, light, heat, chemicals - chemical signals are called ligands signal transduction pathway: sequence of events at molecular level that result in a cell’s response to a signal at its receptor

3. Types of Signal Categories autocrine: affect same cell that releases it; example: cancer cells affecting their own rate of cell division (no distance: remember the immune system example where touching cells transmitted information) paracrine (short distance): travel via diffusion to nearby cells; example: neurotransmitters going from nerve cell to next nerve cell hormones (long distance): travel via circulation to distant cells; example: thyroid stimulating hormone produced by pituitary gland in brain stimulates thyroid in neck to produce thyroid hormone, which affects metabolism in all other body tissues

4. Neurotransmitters: a cascade of reactions Example: The sight, smell and taste of food can cause the vagus nerve to release the neurotransmitter acetylcholine, which binds to receptors on parietal cells, causing an influx of calcium ions that activate intracellular phosphokinase enzymes; this in turn results in the activation of a proton pump to expel hydrogen ions, which can then combine with chloride ions to form the hydrochloric acid that is required for the digestion of food in the stomach.

6. Most pathways are controlled allosterically allosteric regulation: protein’s shape is altered when a molecule binds somewhere other than the active site (remember, this is non-competitive inhibition) - example: ligand-gated channel

7. Ligand binding is reversible • This is necessary to prevent receptors from being continuously blocked • Ligand binding can be blocked by competitive inhibitors - Example: atropine blocks acetylcholine from binding and can be used to counter nerve gas effects (nerve gas alters the activity of the enzyme that controls acetylcholine)

8. Other chemicals can interfere with communication pathways

9. Cocaine and amphetamines inhibit the re-uptake of dopamine. Cocaine is a dopamine transporter blocker that competitively inhibits dopamine uptake to increase the presence of dopamine. • Amphetamine increases the concentration of dopamine in the synaptic gap, but by a different mechanism. Amphetamines are similar in structure to dopamine, and so can enter the presynaptic neuron via its dopamine transporters. By entering, amphetamines force dopamine molecules out of their storage vesicles.

10. 2 Categories of Receptors Cytoplasmic receptors • for the nonpolar, small ligands that can cross the cell membrane • example: tyrosine kinases Membrane receptors • for the polar, large ligands that cannot cross the membrane • example: insulin

11. Types of Membrane Receptors in Eukarya • Ion channel receptors (change shape): gated channels that control the movement of ions - example: acetylcholine neurotransmitter binding to receptor triggers influx of Na+, which eventually leads to contraction of muscle

12. Protein kinase receptors (change shape): binding initiates a reaction chain to occur on cytoplasmic side of cell • The resulting reaction chain modifies a protein by adding phosphate (phosphorylation) • Phosphorylated proteins have a changed shape and therefore a changed function • These changed proteins are incredibly important in regulating cell responses • Insulin binding to protein kinase receptor on membrane results in phosphorylated proteins, which cause the cell to insert glucose transport proteins into the membrane, which allow glucose into the cell

13. Figure 5.13 A Protein Kinase Receptor

14. G protein-linked receptors:ligand binding to receptor causes receptor to bind to G protein on cytoplasmic side; G protein binding activates effector protein • Result of this pathway: the effector protein catalyzes the conversion of many, many reactants into products; “amplification” of the signal • Pathway uses guanine instead of adenine in energy molecules (GDP/GTP instead of ADP/ATP)

16. G protein-linked animation http://bcs.whfreeman.com/hillis1e/#667501__674132__

17. These chain reactions are called … … signal transduction pathways or signaling cascades.

18. Pathways sometimes require an intermediate molecule • “Second messengers” distribute and amplify the signal • they regulate enzymes by binding to them - either expose the active site (activate) or cover it (inhibit) • example: adrenaline (norepinephrine) hormone binding eventually activates a liver enzyme that causes stored glycogen to be broken down into glucose for release; a second messenger is required to get the signal from the membrane receptor to the cytoplasm • Cyclic AMP (cAMP) is a second messenger • cAMP is made from G protein-linked receptor pathway

19. Fight or Flight Response Pathway http://bcs.whfreeman.com/hillis1e/#667501__674133__

21. Figure 5.17 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)

22. How do we control these crazy pathways? • Break down the enzymes • Synthesize other enzymes that change the balance • Inhibit the enzymes • Activate other enzymes

23. In general, how do cells respond to these crazy pathways? • Opening ion channels: changes electrical potential across membranes • Altering their gene expression: switching genes on or off • Altering enzyme activity: activation or inhibition • The same signal can produce different responses in different types of cells