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

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Gidon, Alexandre | Al-Bataineh, Mohammad | Jean-Alphonse, Frédéric | Stevenson, Hilary | Watanabe, Tomoyuki | Louet, Claire | Khatri, Ashok | Calero, Guillermo | Pastor-Soler, Núria | Gardella, Thomas | Vilardaga, Jean-Pierre

Edité par CCSD ; Nature Publishing Group -

International audience. 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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