N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization

TY - JOUR

T1 - N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization

AU - Nørskov-Lauritsen, Lenea

AU - Jørgensen, Stine

AU - Bräuner-Osborne, Hans

N1 - Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

PY - 2015/2/27

Y1 - 2015/2/27

N2 - Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. However, our knowledge about post-translational modifications of class C G protein-coupled receptors and how these modifications regulate expression and function is very limited. Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed.

AB - Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. However, our knowledge about post-translational modifications of class C G protein-coupled receptors and how these modifications regulate expression and function is very limited. Herein, we show that the nutrient-sensing class C G protein-coupled receptor GPRC6A carries seven N-glycans and that one of these sites modulates surface expression whereas mutation of another site affects receptor function. GPRC6A has been speculated to form covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed.

U2 - 10.1016/j.febslet.2015.01.019

DO - 10.1016/j.febslet.2015.01.019

M3 - Journal article

C2 - 25617829

SN - 0014-5793

VL - 589

SP - 588

EP - 597

JO - FEBS Letters

JF - FEBS Letters

ER -