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

Abstract

Metabolic disease: Apprehending an appetite adjuster A molecular ‘chaperone’ helps regulate an essential metabolic signaling protein by ensuring that the protein is in the right place at the right time. The melanocortin-4 receptor (MC4R) controls food intake and energy burning. Abnormal MC4R activity is strongly linked with obesity. Little is known about how this protein is regulated, but researchers led by Ja-Hyun Baik at Korea University, Seoul, South Korea, have identified a potentially important partner for MC4R. They determined that MC4R binds a so-called ‘chaperone’ protein, GRP78, which facilitates trafficking of this receptor from the cell membrane, where it can engage in active signaling, to the cell interior. The researchers showed that GRP78 helps cells cope with cellular stress associated with metabolic disease. Absence of this protein increases sensitivity to diet-induced obesity in mice, indicating a possible target for drug development.