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Gatekeepers Controlling GPCR Export and Function.

Stéphane Doly¹, Stefano Marullo¹

¹Institut Cochin, INSERM, CNRS, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Trends in Pharmacological Sciences

|October 6, 2015

Summary

This summary is machine-generated.

Prenylated Rab acceptor family 2 (PRAF2) retains G protein-coupled receptors (GPCRs) like GABA-B1 in the ER. Interaction with GABA-B2 releases GABA-B1, enabling cell surface progression and impacting disease.

Keywords:

G protein-coupled receptors GABA(B) receptor endoplasmic reticulum gatekeeper prenylated Rab acceptor family 2 regulated export γ-aminobutyric acid

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Published on: March 10, 2020

Area of Science:

Cell Biology
Neuroscience
Molecular Biology

Background:

G protein-coupled receptors (GPCRs) require regulated transport from intracellular compartments to the cell surface.
This process involves chaperones, escort proteins, and gatekeepers that control receptor trafficking.
γ-aminobutyric acid (GABA)B receptors, a heterodimer of GB1 and GB2 subunits, exemplify this regulated export, with GB1 retention in the endoplasmic reticulum (ER).

Purpose of the Study:

To investigate the role of prenylated Rab acceptor family 2 (PRAF2) as an ER-resident gatekeeper in retaining the GB1 subunit of the GABA-B receptor.
To elucidate the mechanism by which GB1 is released from PRAF2 for cell surface progression.
To explore the broader implications of Yip proteins in GPCR trafficking and human diseases.

Main Methods:

Utilized biochemical and cell biological approaches to study protein-protein interactions and receptor trafficking.
Investigated the interaction between PRAF2 and the GB1 subunit in the ER.
Examined the effect of GB2 co-expression on GB1 retention by PRAF2.

Main Results:

Identified PRAF2 as a specific ER-resident gatekeeper responsible for retaining the GB1 subunit.
Demonstrated that GB1 is released from PRAF2 only upon competitive interaction with the GB2 subunit.
Showed that PRAF2 belongs to the mammalian Ypt-interacting protein (Yip) family.

Conclusions:

PRAF2 acts as a crucial gatekeeper for GB1 retention in the ER, preventing premature entry into the biosynthetic pathway.
The interaction between GB1 and GB2 is essential for releasing GB1 from PRAF2-mediated retention.
Yip proteins may regulate the trafficking of various GPCRs, suggesting their potential involvement in diseases linked to impaired receptor cell surface targeting.