Transduction of the chemotactic cAMP signal across the plasma membrane of Dictyostelium cells.
Aggregating Dictyostelium cells secrete cAMP during cell aggregation. cAMP induces two fast responses, the production of more cAMP (relay) and directed cell locomotion (chemotaxis). Extracellular cAMP binds to G-protein-coupled receptors leading to the activation of second messenger pathways, including the activation of adenylyl cyclase, guanylyl cyclase, phospholipase C and the opening of plasma membrane Ca2+ channels. Many genes encoding these sensory transduction proteins have been cloned and null mutants of nearly all components have been characterized in detail. Undoubtedly, activation of adenylyl cyclase is the most complex, involving G-proteins, a soluble protein called CRAC and components of the MAP kinase pathway. Null mutants in this pathway do not aggregate, but can exhibit chemotaxis and develop normally when supplied with exogenous cAMP. The pathways leading to the activation of phospholipase C were identified, but unexpectedly, deletion of the phospholipase C gene has no effect on chemotaxis and development, nor on intracellular Ins(1,4,5)P3 levels; the metabolism of this second messenger will be discussed in some detail. Activation of guanylyl cyclase is G-protein-dependent and essential for chemotaxis. Analysis of a collection of chemotactic mutants reveals that most mutants are defective in either the production or intracellular detection of cGMP, thereby placing this second messenger at the center of chemotactic signal transduction. Analysis of the cAMP-mediated opening of plasma membrane calcium channels in signal transduction mutants suggests that it has two components, one that depends on G-proteins and intracellular cGMP and one that is G-protein-independent.
Department of Biochemistry, University of Groningen, The Netherlands.
P J
PJ
Van Haastert
D000262:Adenylyl Cyclases / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D004023:Dictyostelium / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D011953:Receptors, Cyclic AMP / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000235:genetics
D007295:Inositol Phosphates; D011953:Receptors, Cyclic AMP; D000242:Cyclic AMP; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D006152:Cyclic GMP; D002118:Calcium