The truncated ghrelin receptor polypeptide (GHS-R1b) is localized in the endoplasmic reticulum where it forms heterodimers with ghrelin receptors (GHS-R1a) to attenuate their cell surface expression
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AbstractThe ghrelin receptor (GHS-R1a) is remarkable amongst G-protein-coupled receptors for its high degree of constitutive activity, and this agonist-independent activity may be important for its physiological function in the control of food intake and body weight. Ghrelin receptors form heterodimers with the truncated ghrelin receptor polypeptide (GHS-R1b), which has a dominant-negative effect on ghrelin receptor function. Here we show that GHS-R1b has an intracellular localization distinct from ghrelin receptors, being primarily localized in the endoplasmic reticulum. Immunocytochemical studies suggest that GHS-R1b decreases the plasma membrane expression of ghrelin receptors, but the overall distribution profile of ghrelin receptors in isolated subcellular fractions is unaffected by GHS-R1b. Using bioluminescence resonance energy transfer methods, we have shown that while ghrelin receptor homodimers are evenly distributed in all subcellular fractions, GHS-R1a/GHS-R1b heterodimers are concentrated within the endoplasmic reticulum and these results suggest that GHS-R1b traps ghrelin receptors within the endoplasmic reticulum by the process of oligomerization. Furthermore, ghrelin receptors constitutively activated extracellular signal-regulated kinases 1/2 in the endoplasmic reticulum, but this small response was not affected by GHS-R1b and its physiological relevance is uncertain. Taken together, these results suggest that ghrelin receptors can be retained in the endoplasmic reticulum by heterodimerization with GHS-R1b, and constitutive activation of phospholipase C is attenuated due to decreased cell surface expression of ghrelin receptors. However, sufficient ghrelin receptor homodimers can still be expressed on the cell surface for maximal responses to agonist stimulation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
All Author(s) ListChow KBS, Sun JX, Chu KM, Cheung WT, Cheng CHK, Wise H
Journal nameMolecular and Cellular Endocrinology
Detailed descriptionTo ORKTS: doi: 10.1016/j.mce.2011.08.034
Year2012
Month1
Day2
Volume Number348
Issue Number1
PublisherELSEVIER IRELAND LTD
Pages247 - 254
ISSN0303-7207
LanguagesEnglish-United Kingdom
KeywordsDominant-negative mutant; Ghrelin receptor; GHS-R1b; Heterodimerization
Web of Science Subject CategoriesCell Biology; CELL BIOLOGY; Endocrinology & Metabolism; ENDOCRINOLOGY & METABOLISM

Last updated on 2020-03-07 at 00:53