Functional Evaluation of SLITRK1 Mutations

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Grice, Dorothy, MD

There is strong evidence that Tourette Syndrome (TS) has a genetic etiology, although determining the specific genetic factors involved with TS has been challenging. Recently, in a small number of families, mutations in a gene called SLITRK1 were implicated as being associated with TS and related disorders, such as obsessive-compulsive disorder and trichotillomania. The identification of the SLITRK1 gene as a potential cause of TS demands follow-up directed at exploring the pathways in which SLITRK1 functions in the brain. Identifying and elucidating such pathways may lead to a better understanding of the developmental abnormalities that underlie TS, and may lead to additional genes that contribute to the manifestation of TS symptoms. In the current proposal we detail cellular and molecular studies on SLITRK1 and SLITRK1-related pathways. We have associated a cellular pathway called the ERK/MAP kinase cascade with SLITRK1. We have also discovered that SLITRK1 can be cleaved by specific enzymes in the cell and that this cleavage process likely plays a significant role in the activation of SLITRK1-related pathways. In this proposal we will continue to characterize the components and functions of the SLITRK1 pathway, and will determine whether mutations in the SLITRK1 gene affect any of these important biological processes involving SLITRK1 function. With the completion of these studies we predict that there will be significant advances in understanding the biology of SLITRK1, which in turn, could lead to a greater understanding of the biology of TS. Dorothy E. Grice, M.D. Mount Sinai School of Medicine New York, NY Award: $55,000 This Award is funded by Ralph Ochsman and The Ochsman Foundation. Tourette Association of America Inc. – Research Grant Award 2007-2008