From GTP and G proteins to TRPC channels: a personal account

• Autores: Birnbaumer, Lutz
• Año de publicación: 2015
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Ca Signaling; G Protein-Coupled Receptor; G Proteins; Gtpase; Transient Receptor Potential Channel
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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 Mg2+. 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.
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. National Institute of Environmental Research; Estados Unidos