title: G protein-coupled receptor signaling via Src kinase induces endogenous human transient receptor potential vanilloid type 6 (TRPV6) channel activation.
abstract: Ca(2+) homeostasis plays a critical role in a variety of cellular processes. We showed previously that stimulation of the prostate-specific G protein-coupled receptor (PSGR) enhances cytosolic Ca(2+) and inhibits proliferation of prostate cells. Here, we analyzed the signaling mechanisms underlying the PSGR-mediated Ca(2+) increase. Using complementary molecular, biochemical, electrophysiological, and live-cell imaging techniques, we found that endogenous Ca(2+)-selective transient receptor potential vanilloid type 6 (TRPV6) channels are critically involved in the PSGR-induced Ca(2+) signal. Biophysical characterization of the current activated by PSGR stimulation revealed characteristic properties of TRPV6. The molecular identity of the involved channel was confirmed using RNA interference targeting TrpV6. TRPV6-mediated Ca(2+) influx depended on Src kinase activity. Src kinase activation occurred independently of G protein activation, presumably by direct interaction with PSGR. Taken together, we report that endogenous TRPV6 channels are activated downstream of a G protein-coupled receptor and present the first physiological characterization of these channels in situ.
authors.affiliation: Department of Chemosensation, RTWH Aachen University, 52074 Aachen, Germany. j.spehr@sensorik.rwth-aachen.de
authors.forename: Jennifer
authors.initials: J
authors.lastname: Spehr
authors.forename: Lian
authors.initials: L
authors.lastname: Gelis
authors.forename: Markus
authors.initials: M
authors.lastname: Osterloh
authors.forename: Sonja
authors.initials: S
authors.lastname: Oberland
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
authors.forename: Marc
authors.initials: M
authors.lastname: Spehr
authors.forename: Eva M
authors.initials: EM
authors.lastname: Neuhaus
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008297:Male; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D043562:Receptors, G-Protein-Coupled; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; D019061:src-Family Kinases; D002118:Calcium