Principles of Cell Signaling

Principles of Cell signaling Side Notes: Cell communication = cell signaling Most cells in multicellular organisms can emit and receive signals Cells communicate through signaling molecules Receptor proteins bind the signaling molecules Binding activates intracellular signaling pathway, which leads to a change in cell behavior Signaling pathway = signal transduction pathway Why do animal cells need to communicate? Development Immune responses Homeostasis Cell division Cell survival and cell death Learning and memory Most signaling proteins and receptors were conserved in evolution Studies of yeast mutants unable to mate helped identify proteins involved in signaling These proteins have homologs in animal cells Animal proteins, involved in signaling are grouped into families highly conserved in evolution Many of these proteins were first discovered in Drosophilia fly, and C. elegans worm Which of the following can diffuse through the plasma membrane and does not require channels? • CO2 • H2O • K+ What is the signal? There are hundreds of kinds of signaling molecules. They include: proteins small peptides amino acids nucleotides steroids, retinoids fatty acid derivatives dissolved gases (NO, CO) Signals can bind to cell surface receptor or diffuse through plasma membrane and bind inside the cell Four forms of intracellular signaling Contact-dependent Paracrine Synaptic Endocrine Contact-dependent Important in development and immune responses Cells can extend long processes that can stretch for a few cell lengths Paracrine signaling Signaling molecules do not spread very far: They can be quickly absorbed by other cells Get degraded by extracellular enzymes Principles of cell signaling Side Notes: Autocrine signaling is analogous to _____ • A telephone conversation • Talking to people at a cocktail party • A radio announcement • Talking to yourself Get trapped in extracellular matrix Paracrine signaling plays a role in development, proliferation, cell survival, immune responses, tissue repair, etc. Similar sets of highly conserved signals and receptors are used Four major families based on similar structures: Fibroblast growth factor (FGF) family (primarily in proliferation and differentiation) Hedgehog family (mostly in development) Wnt family (development, cell adhesion, cell proliferation, etc.) TGF-beta superfamily (mostly in development) Synaptic signaling Neuron gets activated by stimuli from other cells or environment Sends signal (action potential) along its axon Signal reaches the synapse Neurotransmitter is released Neurotransmitter binds to receptors on target cell (process takes less than millisecond) Neurotransmitters Amino acids Glutamate, gamma-aminobutyric acid (GABA), glycine, etc. Monoamines Dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), serotonin, etc. Peptides Somatostatin p, opioid peptides, etc. Others Acetylcholine, anandamide, nitric oxide, etc. Endocrine signaling Endocrine cells secrete hormones into the bloodstream Hormones travel one distances through bloodstream to reach their target cells Hormones Peptide hormones Insulin, growth hormone, etc. Lipid and phospholipid-derived hormones Steroid hormones (testosterone, progesterone, estrogen, cortisol, etc.) Monoamines Adrenaline (both hormone and neurotransmitter) Comparison of endocrine and synaptic signaling mechanisms Endocrine Slow Relies on diffusion and blood flow Low concentration signal Hormones are low concentration in blood High affinity of receptors Synaptic Fast Principles of Cell Signaling Side Notes: Electrical impulse 100 m/sec, diffusion of neurotransmitter over less than 100 nm High concentration signal High concentration of neurotransmitter at synapse Low affinity of receptors Neurotransmitter needs to dissociate rapidly The target cell can respond to a signal slow or rapidly Which of the receptors have the lowest affinity to their signaling molecules? • Receptors for steroid hormones • Acetylcholine receptors in the synapse • Ligand-receptor pair involved in contactdependent signaling Different cells respond differently to the same signal molecule An animal cell behavior depends on the combination of signals it receives How are extracellular signals turned off? Some signals are enzymatically degraded Active removal by transporters (ion pumps);this is typical for many neurotransmitters Diffusion, dilution, degradation: typical for hormones Short half life due to interaction with other molecules (NO, CO) Shutting different components of signal transduction pathway