aVLFZ041 Selected lectures from Physiology1 Receptors: key structures in cell signaling Tibor Stračina stracina@med.muni.cz 2 The presentation is copyrighted work created by employees of Masaryk University. Any unauthorised reproduction or distribution of the presentation or individual slides is against the law. aVLFZ041 Selected lectures from Physiology3 Signal transduction in multicellular organism ̶ Humoral signaling ̶ Neuronal signaling aVLFZ041 Selected lectures from Physiology4 Signal transduction in multicellular organism ̶ Humoral signaling ̶ Neuronal signaling ? aVLFZ041 Selected lectures from Physiology5 Signal transduction in multicellular organism ̶ Humoral signaling ̶ Neuronal signaling ? aVLFZ041 Selected lectures from Physiology6 Cellular signaling signal transduction response https://www.cellsignal.com/contents/science-cst-pathways-cellular-metabolism/insulin-receptor-signaling/pathways-irs aVLFZ041 Selected lectures from Physiology7 Cellular signaling signal transduction response Receptors https://www.cellsignal.com/contents/science-cst-pathways-cellular-metabolism/insulin-receptor-signaling/pathways-irs aVLFZ041 Selected lectures from Physiology8 Receptors ̶ Protein-based structures ̶ Receive and transduce signals ̶ Integrated in signaling pathways aVLFZ041 Selected lectures from Physiology9 Classification ̶ Location: ̶ Intracellular ̶ Cell surface ̶ Function ̶ Ionotropic = ligand-gated ion channels ̶ G protein-coupled ̶ Enzyme-linked Tyrosine kinases Histidine kinases aVLFZ041 Selected lectures from Physiology10 Intracellular vs. cell-surface receptors aVLFZ041 Selected lectures from Physiology11 Ionotropic receptors ̶ Ligand-gated ion channels ̶ Direct change of membrane voltage and/or intracellular concentration of the ion aVLFZ041 Selected lectures from Physiology12 Metabotropic receptors ̶ Production of second messenger ̶ G protein-coupled receptors ̶ Enzyme-linked receptors ̶ Receptor Tyrosine kinases ̶ Receptor Histidine kinases aVLFZ041 Selected lectures from Physiology13 G protein-coupled receptors ̶ Production of second messenger: cAMP, cGMP, DAG, IP3, Ca2+ ̶ Gs ̶ Gi ̶ Gq https://www.khanacademy.org/science/biology/cell-signaling/mechanisms-of-cell-signaling/a/signal-perception aVLFZ041 Selected lectures from Physiology14 Enzyme-linked receptors Receptor tyrosine kinases ̶ Tyrosine kinase activity phosphorilation of enzymes/other proteins https://ars.els-cdn.com/content/image/3-s2.0-B9780124059269000046-f04-04-9780124059269.jpg?_ aVLFZ041 Selected lectures from Physiology15 Regulation of receptor response Down-regulation ̶ Decrease of number and/or sensitivity of the receptors due to increased ligand stimulation ̶ Desensitisation ̶ Internalisation aVLFZ041 Selected lectures from Physiology16 Regulation of receptor response Up-regulation ̶ Increase of number and/or sensitivity of the receptors due to decreased ligand stimulation ̶ (Re)sensitisation ̶ Externalisation ̶ Synthesis de novo aVLFZ041 Selected lectures from Physiology17 Receptor families ̶ Classification according to ligand(s) aVLFZ041 Selected lectures from Physiology18 Adrenergic receptors ̶ G protein-coupled receptors ̶ Subtypes: ̶ Alpha: α1 (Gq) – DAG+IP3; smooth muscle contraction, mydriasis α2 (Gi) – cAMP; platelet activation ̶ Beta (Gs) - cAMP β1 – heart (SA node) β2 – smooth muscle relaxation (bronchodilation) β3 – lipolysis, urination aVLFZ041 Selected lectures from Physiology19 Acetylcholine (cholinergic) receptors ̶ M type = Muscarinic acetylcholine receptors ̶ Metabotropic receptors – G-protein coupled receptors ̶ Subtypes M1 – CNS, autonomic ganglia, salivary glands, stomach M2 – heart (SA node, atria, AV node), CNS M3 – smooth muscle (e.g. vessels, bronchi), endocrine+exocrine glands, GIT, eyes, CNS M4+M5 – CNS ̶ N type = Nicotinic acetylcholine receptors ̶ Ionotropic receptors – ligand-gated ion channels ̶ Subtypes (according to subunits) Nm – „muscular“ type – neuromuscular junction Nn – „neuronal“ type – autonomic ganglia, adrenal medulla aVLFZ041 Selected lectures from Physiology20 Insulin receptors https://www.cellsignal.com/contents/science-cst-pathways-cellular-metabolism/insulin-receptor-signaling/pathways-irs aVLFZ041 Selected lectures from Physiology21 VEGFR ̶ Vascular endothelial growth factor receptor aVLFZ041 Selected lectures from Physiology22 IP3 receptors ̶ Inositol-tris-phosphate receptors aVLFZ041 Selected lectures from Physiology23 Sigma receptors Sigma receptors Sigma receptor type 2 Sigma receptor type 3 (?) Sigma receptor type 1 • well-characterized • molecular chaperone • Ca2+ handling modulation • various protein-protein interactions • motor control • over-expressed in various types of tumor cells • less-known • immune system aVLFZ041 Selected lectures from Physiology24 Sigma 1 R Su et al., 2016. Trends Pharmacol Sci. 2016; 37(4): 262–278. doi:10.1016/j.tips.2016.01.003 aVLFZ041 Selected lectures from Physiology25 Take home messege Receptors are ̶ crucial structures in cell signalling. ̶ important in pathophysiology of many diseases. ̶ targets of pharmacotherapy. 26 The presentation is copyrighted work created by employees of Masaryk University. Any unauthorised reproduction or distribution of the presentation or individual slides is against the law.