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Cell Communication Cell SignalingAnimal cells communicate by:-direct contact (gap junctions)-secreting local regulators (growth factors, neurotransmitters)-long distance (via hormones) 3 Stages of Cell Signaling:1. Reception: detection of a signal molecule (ligand) coming from outside the cell2. Transduction: convert signal to a form that can bring about a cellular response3. Response: cellular response to the signal molecule 1. RECEPTION-binding between signal molecule (ligand) + receptor is highly specific-types of receptors: --plasma membrane receptor: water-soluble ligands --intracellular receptors (cytoplasm, nucleus): hydrophobic or small ligands ex: testosterone or nitric oxide (NO)-ligand binds receptor protein à prot changes shape à initiates transduction signal-Plasma membrane receptors: --G-protein coupled receptor (GPCR): 7 transmembrane segments in membrane à signal binds à activates receptor à activates G protein + GTP à activates enzyme à results in cell response --Tyrosine kinase: receptor tyrosine kinase monomers (unphosphorylated) à signal binds à receptor molecules dimerize à activate tyr kinase regions à phosphorylate à activate relay proteins à result in multiple cellular responses --Ligand-gated ion channels: signal on receptor changes shape. Signaling molecule binds àion channel opens à allows entry of ions (like Ca2+ or Na+) à leads to cell response 2. TRANSDUCTION-Cascades of molecular interactions relay signals from receptors à target molecules-Protein Kinase: enzyme that phosphorylates and activates proteins at next level-Phosphorylation cascade: enhance and amplify signal-Second Messengers: small non-protein molecules/ions that can relay signal inside cell (ex: cyclic AMP, calcium ions, inositol triphosphate) --cyclic AMP (cAMP) = cyclic adenosine monophosphateGPRC à adenylyl cyclase (convert ATP à cAMP) à activate protein kinase A 3. RESPONSE-regulate protein synthesis by turning on/off genes in nucleus (gene expression)-regulate proteins in cytoplasm Signal pathway transduction problems/defects:-examples: diabetes, cholera, autoimmune disease, cancer, neurotoxins, poisons, pesticides, drugs (anesthetics, antihistimines, blood pressure meds) --cholera example -disease acquired by drinking contaminated water (w/ human feces)-vibrio cholera bacteria colonizes lining of small intestine and produces toxin-toxin modifies G-protein involved in regulating salt and water secretion -G protein stuck in active form à intestinal cells secrete salts, water--infected person develops profuse diarrhea and could die from loss of water and salts Apoptosis = programmed cell death-cell is dismantled and digested-triggered by signals that activate cascade of cell death proteins (caspase)-why: protect neighboring cells from damage. Animal development and maintenance-may be involved in some diseases (Parkinson’s, Alzheimer’s)
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