Endosomal GPCR signaling turned off by negative feedback actions of PKA and v-ATPase

July 27th, 2014 by Alexandre Gidon

Nature Chemical Biology 10, 707 (2014). doi:10.1038/nchembio.1589

Authors: Alexandre Gidon, Mohammad M Al-Bataineh, Frederic G Jean-Alphonse, Hilary P Stevenson, Tomoyuki Watanabe, Claire Louet, Ashok Khatri, Guillermo Calero, Núria M Pastor-Soler, Thomas J Gardella & Jean-Pierre Vilardaga

The PTH receptor is to our knowledge one of the first G protein–coupled receptor (GPCR) found to sustain cAMP signaling after internalization of the ligand–receptor complex in endosomes. This unexpected model is adding a new dimension on how we think about GPCR signaling, but its mechanism is incompletely understood. We report here that endosomal acidification mediated by the PKA action on the v-ATPase provides a negative feedback mechanism by which endosomal receptor signaling is turned off.

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