Glucose-regulated protein 78 binds to and regulates the melanocortin-4 receptor

Ye Ran Yoon, Tae Gul Lee, Mi Hyun Choi, Seung Woo Shin, Young-Gyu Ko, Im Joo Rhyu, Dong-Hun Kim, Je Kyung Seong, Ja-Hyun Baik

Research output: Contribution to journalArticle

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.

Original languageEnglish
Number of pages1
JournalExperimental & molecular medicine
Volume50
Issue number9
DOIs
Publication statusPublished - 2018 Sep 12

Fingerprint

Receptor, Melanocortin, Type 4
Paraventricular Hypothalamic Nucleus
Small Interfering RNA
Receptor-Interacting Protein Serine-Threonine Kinases
Tunicamycin
Endoplasmic Reticulum Stress
glucose-regulated proteins
High Fat Diet
Nutrition
G-Protein-Coupled Receptors
Cell Communication
Cytosol
Hypothalamus
Assays
Homeostasis
Down-Regulation
Fats
Body Weight

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Glucose-regulated protein 78 binds to and regulates the melanocortin-4 receptor. / Yoon, Ye Ran; Lee, Tae Gul; Choi, Mi Hyun; Shin, Seung Woo; Ko, Young-Gyu; Rhyu, Im Joo; Kim, Dong-Hun; Seong, Je Kyung; Baik, Ja-Hyun.

In: Experimental & molecular medicine, Vol. 50, No. 9, 12.09.2018.

Research output: Contribution to journalArticle

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AU - Ko, Young-Gyu

AU - Rhyu, Im Joo

AU - Kim, Dong-Hun

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