Da Silva, E.; Scott, M.G.H.; Enslen, H.; Marullo, S. Control of CCR5 Cell-Surface Targeting by the PRAF2 Gatekeeper. Int. J. Mol. Sci.2023, 24, 17438.
Da Silva, E.; Scott, M.G.H.; Enslen, H.; Marullo, S. Control of CCR5 Cell-Surface Targeting by the PRAF2 Gatekeeper. Int. J. Mol. Sci. 2023, 24, 17438.
Da Silva, E.; Scott, M.G.H.; Enslen, H.; Marullo, S. Control of CCR5 Cell-Surface Targeting by the PRAF2 Gatekeeper. Int. J. Mol. Sci.2023, 24, 17438.
Da Silva, E.; Scott, M.G.H.; Enslen, H.; Marullo, S. Control of CCR5 Cell-Surface Targeting by the PRAF2 Gatekeeper. Int. J. Mol. Sci. 2023, 24, 17438.
Abstract
The cell surface targeting of neo-synthesized G protein coupled receptors (GPCRs) involves recruitment of receptor into COPII vesicles budding at Endoplasmic Reticulum Exit sites (ERES). This process is regulated for some GPCRs by escort proteins, which facilitate their export, or by gatekeepers that retain the receptors in the ER. PRAF2, an ER gatekeeper of the heterodimeric GABAB receptor protomer GB1, which interacts with a tandem di-leucine / RXR retention motif in the carboxyterminal tail of GB1, also inhibits the plasma membrane export of the chemokine receptor CCR5. PRAF2 / CCR5 interactions involve the transmembrane domains of both proteins. The di-leucine / RXR motif contained in the third intracellular loop of CCR5 does not affect PRAF2-mediated retention but impairs instead the interaction between CCR5 and its private escort protein CD4. PRAF2 and CD4 thus display opposite roles on the cell surface export of CCR5, likely at the level of its recruitment into COPII vesicles, PRAF2 inhibiting and CD4 promoting this process.
Biology and Life Sciences, Biochemistry and Molecular Biology
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