Glucose-regulated protein 78 binds to and regulates the melanocortin-4 receptor.
Exp Mol Med
; 50(9): 1-14, 2018 09 12.
Article
in En
| MEDLINE
| ID: mdl-30209265
ABSTRACT
The melanocortin-4 receptor (MC4R) belongs to the G protein-coupled receptor (GPCR) family and plays an essential role in the control of energy homeostasis. Here, we identified a novel MC4R-interacting protein, glucose-regulated protein 78 (GRP78), from a pulldown assay using hypothalamic protein extracts and the third intracellular loop of MC4R. We found that MC4R interacted with GRP78 in both the cytosol and at the cell surface and that this interaction increased when MC4R was internalized in the presence of the agonist melanotan-II (MTII). Downregulation of GRP78 using a short interfering RNA approach attenuated MTII-mediated receptor internalization. Reduction in GRP78 expression during tunicamycin-induced endoplasmic reticulum stress also suppressed MTII-mediated internalization of MC4R and cAMP-mediated transcriptional activity. Furthermore, lentiviral-mediated short hairpin RNA knockdown of endogenous GRP78 in the paraventricular nucleus (PVN) of the hypothalamus resulted in an increase in body weight in mice fed a high-fat diet. These results suggest that GRP78 in the PVN binds to MC4R and may have a chaperone-like role in the regulation of MC4R trafficking and signaling.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptor, Melanocortin, Type 4
/
Heat-Shock Proteins
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Exp Mol Med
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2018
Document type:
Article
Affiliation country:
South Korea