| Autor: |
Kathleen M. Caron, Duncan I. Mackie, Asuka Inoue, Denise Wootten, John B. Pawlak, Mark Soave, Matthew Harris, Ho Yan Yeung, Suleiman Al-Sabah, Matthew T. Harper, Stephen J. Briddon, Graham Ladds, Peishen Zhao, Sabrina Carvalho, Dewi Safitri, Patrick M. Sexton, David R. Poyner, Sarah J Routledge, Stephen J. Hill, Bashaier Al-Zaid, Tin T. Truong |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.04.08.436756 |
| Popis: |
Gastric inhibitory polypeptide (GIP) receptor is a class B1 GPCR, that responds to GIP and physiologically potentiates glucose-stimulated insulin secretion. Like most class B1 GPCRs, GIPR has been shown to interact with RAMPs, yet the effects of RAMPs on its signalling and trafficking remain poorly understood. We demonstrate that RAMPs modulate G protein activation and GIPR internalisation profiles. RAMP3 reduced GIPR Gsactivation and cAMP production but retained GIPR at the cell surface, and this was associated with prolonged ERK1/2 phosphorylation and β-arrestin association. By contrast, RAMP1/2 reduced Gq/11/15activation of the GIPR. Through knockout mice studies, we show that RAMP1 is important to the normal physiological functioning of GIPR to regulate blood glucose levels. Thus, RAMPs act on G protein/β-arrestin complexes, having both acute and chronic effects on GIPR function, while this study also raises the possibility of a more general role of RAMP3 to enhance GPCR plasma membrane localisation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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