Biology 325 Fall 2004 Cell signaling I Introduction types of intercellular communication A Gap junctions important in excitable tissue where tissue is a functional syncythium cardiac muscle and smooth muscle B Transient direct linkup of cells macrophage helper T cell interactions in immune cell function Figure 12 17 C Paracrine secretion local chemical messengers released by a cell that affect neighboring cells not systemic histamine release by mast cells in connective tissue VEGF release by neural cells in retina D Neurotransmitter secretion synaptic transmission neuromuscular junction E Hormonal secretion thyroid hormone release gonadotrophin release by anterior pituitary F Neurohormone secretion posterior pituitary hormones ADH oxytocin II Chemical messengers vary in structure amino acids polypeptides proteins glycoproteins steroids mode of action how chemical messenger exerts effect on other cells varies depends on chemical structure of messenger lipid soluble messengers readily diffuse through target cell membranes receptors are cytosolic or even nuclear Figure 18 5 polar hydrophilic hormones will bind receptors usually transmembrane proteins hormone binding to receptors can alter membrane permeability by acting on channel proteins result in production of second messengers that will alter activity of cellular proteins influence cell processes such as cell metabolism secretion contraction shape apoptosis gene expression among others III Extracellular messengers regulation of channel function recall gated channels chemically gated voltage gated mechanically gated A Direct action of chemical messenger on channels ligand binds receptor in this case also a chemically gated channel i e Na K channel altered Na K flow between ECF and cell altered electrical activity effects on cell function such as opening of other channels voltage gated release of ions from intercellular stores B Initiation of membrane signaling cascades ligand receptor is a transmembrane protein ligand receptor binding causes activation of another membrane protein a G protein GTP binding protein active G protein open a channel i e Ca activates cell proteins cell function changes IV Extracellular messengers activation of second messenger systems A cAMP second messenger system ligand binds receptor receptor binds G protein G protein is a trimeric complex subunits in inactive state GDP bound to subunit when receptor binds G protein GDP released from subunit this opens up binding site for GTP GTP binds subunit subunit activated activated subunit breaks from and subunits binds to effector protein in this case adenylate cyclase AC activated AC converts ATP to cAMP activation of protein kinase A initiation of phosphorylation cascade enzyme activation or deactivation i e glycogen phosphorylase and glycogen synthase regulation of glycogen metabolism altered cell function B Inositol phosphate Ca second messenger system first part of system is similar to above ligand binding will cause produce an active Gprotein subunit activated subunit breaks from and subunits binds to effector protein in this case phospholipase C PLC PLC will hydrolyze phosphatidylinositol bisphosphate PIP2 into inositol trisphosphate IP3 and diacylglycerol DAG 1 IP3 is released into cytosol acts on endoplasmic reticulum promoting Ca release leads to further Ca induced Ca release calcium binds to specific proteins calmodulin activating them will phosphorylate and activate other cellular proteins changes in cell function 2 DAG stay within membrane and activates a membrane associated protein protein kinase C PKC PKC will phosphorylate and affect function of variety of other phosphoproteins changes in cell function C Second messenger systems summary transduction of signal across membrane achieved concept of amplification of signal one hormone molecule binding a receptor can ultimately affect function of large number of cellular proteins and dramatically influence cell function reason why most growth factors and hormones are very active at low concentrations