title: From GTP and G proteins to TRPC channels: a personal account.
abstract: By serendipity and good fortune, as a postdoctoral fellow in 1967, I landed at the right place at the right time, as I was allowed to investigate the mechanism by which hormones activate the enzyme adenylyl cyclase (then adenyl cyclase) in Martin Rodbell's Laboratory at the NIH in Bethesda, Maryland. The work uncovered first, the existence of receptors separate from the enzyme and then, the existence of transduction mechanisms requiring guanosine-5'-triphosphate (GTP) and Mg(2+). With my laboratory colleagues first and postdoctoral fellows after leaving NIH, I participated in the development of the field "signal transduction by G proteins," uncovered by molecular cloning several G-protein-coupled receptors (GPCRs) and became interested in both the molecular makeup of voltage-gated Ca channels and Ca2+ homeostasis downstream of activation of phospholipase C (PLC) by the Gq/11 signaling pathway. We were able to confirm the hypothesis that there would be mammalian homologues of the Drosophila "transient receptor potential" channel and discovered the existence of six of the seven mammalian genes, now called transient receptor potential canonical (TRPC) channels. In the present article, I summarize from a bird's eye view of what I feel were key findings along this path, not only from my laboratory but also from many others, that allowed for the present knowledge of cell signaling involving G proteins to evolve. Towards the end, I summarize roles of TRPC channels in health and disease.
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Research, Research Triangle Park, NC, 27009, USA. Birnbau1@gmail.com.|Institute of Biotechnology Research (IIB-INTECH), National University of San Martin (UNSAM), Avenida 25 de Mayo y Francia, San Martin, CP1650, Provincia de Buenos Aires, Argentina. Birnbau1@gmail.com.
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
mesh_terms: D000818:Animals; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D050052:TRPC Cation Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D050052:TRPC Cation Channels; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins
keywords: Ca signaling; G protein-coupled receptor; G proteins; GTPase; transient receptor potential channel