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Biol Aujourdhui. 2018;212(1-2):13-19. doi: 10.1051/jbio/2018018. Epub 2018 Oct 26.

[Internalized receptor for glucose-dependent insulinotropic peptide stimulates adenylyl cyclase on early endosomes].

[Article in French]

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Laboratoire de Physique et Chimie des Nano-objets (LPCNO), équipe RTTC, Université de Toulouse, CNRS, INSA, INSERM, Université Paul Sabatier, 1 avenue Jean Poulhès, 31432 Toulouse cedex, France - INSERM ERL1226, Receptors and Therapeutic Targeting of Cancers, Toulouse, France.


G-protein coupled receptors represent the largest family of membrane receptors. G-protein dependent signal of GPCR is classically thought to originate exclusively from the plasma membrane and, until very recently, internalized GPCRs were considered silent. At present, experimental proofs exist showing that GPCR can continue to signal via G proteins after internalization. We demonstrated that, once internalized in early endosomes, Glucose-dependent Insulinotropic Peptide Receptor (GIPR) continues to stimulate production of cAMP and activate PKA. In addition to indirect proofs showing that kinetics of cAMP production and PKA activation depend on internalization and GIPR trafficking, we identified the active form of Gαs on early endosomes containing GIPR and detected a distinct FRET signal accounting for cAMP production at the surface of endosomes containing GIP, relative to endosomes without GIP.


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