A Study of the Sequestration of Melanin-Concentrating Hormone Receptor-1 in Caveolae: A Potential Mode of Cell Signaling Regulation by an Appetite-Stimulating Hormone

Abstract

The prevalence of obesity in the United States of America has increased over the last twenty years. This prevalence has led to an increase in the study of the hormones involved control of metabolism and satiety to further understand the factors involved in obesity. One of these hormones is melanin-concentrating hormone (MCH). Many of the studies of MCH focus on the brain, while little work is done on the peripheral tissues. In adipose cells stimulation with MCH causes a release of leptin through activation of melanin-concentrating hormone receptor-1, a G-protein coupled receptor. MCHR1 becomes desensitized after activation with MCH, but the method of desensitization is unknown. ELISA studies show that internalization of the receptor is low unless proteins in the clathrin pathway are incorporated, so another method of desensitization must be occurring. Through sucrosegradient centrifugation MCHR1 co-localizes with caveolin-1, suggesting a role for lipid rafts in receptor dynamics. This thesis will examine the extent of interaction between caveolin-1 and MCHR1. The first aim will be to determine the degree of co-localization of receptor and caveolin-1 under varying conditions. The second aim will be to analyze the dynamics of the MCHR1 within caveolae after MCH stimulation and with expression of the arrestins. The goal will be to better understand the interaction between caveolae and MCHR1 and possibly provide insight into MCHR1 's mode of desensitization.