Project Summary

Francis Lee, M.D., Ph.D. (Young Investigator 2005) of Weill Medical College of Cornell University, aims to elucidate the molecular mechanisms of the Trk neurotrophin receptor, a protein on the surface of neurons which responds to neurotrophins, or nerve growth factors, and regulates nerve cell function. Alterations in neurotrophin levels have been implicated in neurodegenerative disorders and psychiatric disorders, such as depression. Dr. Lee hypothesizes that highly specialized biochemical mechanisms regulate trafficking of activated Trk receptors to different intracellular pathways, which determine the biological responses of neurotrophins. Preliminary studies suggest specialized mechanisms of endocytic regulation appear to be mediated by novel protein interactions. The studies proposed in this application aim to establish quantitative trafficking assays that will characterize specific proteins that mediate these sorting mechanisms, and examine the functional consequences of these sorting proteins on the neurotrophin system. Results should lead to a better understanding of neurotrophin receptor regulation, and should inform efforts to utilize the neurotrophin system for treatment of neurodegenerative and psychiatric disorders.

Program Area: MOOD DISORDERS\Unipolar Depression\Neurodegenerative Disorders

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