Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 49
Activated melanocortin 3 receptor is endocytosed and leads to modification of
transcription factor forkhead (Drosophila) homolog (rhabdomyosarcoma) like 1
James M. Wachira, Bindhu Guruswamy, Lawrence C. Uradu and Cleo A. Hughes-
Darden
Department of Biology, Morgan State University, 1700 E. Cold Spring Lane, Baltimore
MD 21251, U.S.A. E.mail: jwachir@morgan.edu, binduguru25@yahoo.com,
lawrenceuradu@yahoo.com, chughes@moac.morgan.edu
Melanocortins play a central role in autonomic modulation of metabolism by acting through a
family of highly homologous G-protein coupled receptors. Studies with gene knockout mice
have implicated melanocortin receptors, MC3R and MC4R, in the etiology of obesity, insulin
resistance and salt-sensitive hypertension. In an attempt to better understand the mechanisms
of function of these receptors, we expressed MC3R and MC4R in neuronal cells and
demonstrated their colocalization to several membrane regions. We now show that in
cultured neuronal cells, MC3R localizes to lipid rafts and undergoes endocytic internalization
upon activation by gamma-MSH through a protein kinase sensitive pathway. The appearance
of the internalized receptor in lysosomes suggests that it is subsequently degraded. The
expression of protein kinase A regulatory subunits and of c-Jun and c-Fos was analyzed by
either immunoblotting or real-time PCR. No discernable changes were observed in the
expression levels of these protein kinase A and protein kinase C responsive genes. However,
an observed modification of the protein kinase B responsive FKHRL1 in MC3R expressing
cells suggests an important role for the PI3K/AKT pathway in melanocortin mediated effects.
Immunohistochemical studies showed a robust expression of MC3R protein in brain nuclei
with relevance to cardiovascular function and fluid homeostasis thereby suggesting that the
physiological effects of melanocortins on the cardiovascular system arise from effects on the
central nervous system.
Supported by MBRS-Score grant #2SO6-GM051971-08 and RCMI grant # G12RR017581.
Lawrence Uradu is supported by NIH/MARC grant #5T34GM007977-21
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