G protein-coupled receptor signaling via Src kinase induces endogenous human transient receptor potential vanilloid

Jennifer Spehr1, Lian Gelis, Markus Osterloh

  • 1Department of Chemosensation, RTWH Aachen University, 52074 Aachen, Germany. j.spehr@sensorik.rwth-aachen.de

Insights

Prostate-specific G protein-coupled receptor (PSGR) stimulation increases intracellular calcium via TRPV6 channels. This study details the in situ physiological characterization of these calcium channels.

Area of Science:

  • Cellular biology
  • Molecular physiology
  • Ion channel function

Background:

  • Calcium (Ca2+) homeostasis is vital for cellular functions.
  • Prostate-specific G protein-coupled receptor (PSGR) stimulation elevates cytosolic Ca2+ and reduces prostate cell proliferation.
  • The signaling pathways mediating PSGR-induced Ca2+ increases require elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms behind PSGR-mediated Ca2+ signaling.
  • To identify the specific ion channels involved in PSGR-induced Ca2+ influx.
  • To characterize the physiological function of these channels in situ.

Main Methods:

  • Utilized a combination of molecular, biochemical, and electrophysiological techniques.
  • Employed live-cell imaging for real-time Ca2+ signal analysis.
  • Used RNA interference (RNAi) to confirm the molecular identity of the channel.

Main Results:

  • Identified endogenous Ca2+-selective transient receptor potential vanilloid type 6 (TRPV6) channels as critical mediators of the PSGR-induced Ca2+ signal.
  • Biophysical properties of the PSGR-activated current matched those of TRPV6 channels.
  • TRPV6-mediated Ca2+ influx was dependent on Src kinase activity, which was activated independently of G protein activation.
  • Confirmed the role of TRPV6 using RNAi targeting TrpV6.

Conclusions:

  • Endogenous TRPV6 channels are activated downstream of a G protein-coupled receptor (PSGR).
  • This study provides the first in situ physiological characterization of TRPV6 channels in this context.
  • PSGR signaling involves TRPV6 and Src kinase, offering insights into prostate cell calcium regulation.

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