Scholars Day: April 11, 2012

Desensitization of MCH Signaling Most Likely Due to Sequestration of Signaling Components Rather Than Removal of Receptors From the Plasma Membrane

Melanin-concentrating hormone (MCH) is an important regulator of appetite and is a target for treatment of eating disorders. The GPCR's for MCH can be found in the central nervous system, gastrointestinal tract and adipose tissue. MCHR1 is thought to desensitize via clathrin-mediated endocytosis. Research performed by our group however, shows that MCHR1 does not internalize efficiently without the assistance of beta-arrestin overexpression. Another desensitization method is probably used for MCHR1. We hypothesize that caveolae play a role in regulating MCH signaling. First, we verified colocalization of MCHR1 to caveolae and then asked whether MCH mediates changes in the localization of receptor to lipid rafts. Results confirmed that MCHR1 is co-localized with caveolin-1 in numerous cell types. Surprisingly, we were unable to detect MCH-mediated changes in the location of MCHR1 on sucrose flotation gradients. We are now transitioning these studies to a more physiologically relevant model system.

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