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Much of human brain development occurs during embryonic stages, when neurons use membrane proteins with extreme precision to wire the brain. Our lab focuses on the Slitrk family of transmembrane proteins, which are found at synaptic sites. Slitrks 1-6 influence neuron morphology and synapse formation during nervous system development. Mutations in these proteins have genome-wide associations with major psychiatric diseases, such as schizophrenia and Tourette syndrome. Slitrk2, specifically, has a large intracellular domain with no studied function. Previous preliminary tests that investigated potential binding partners yielded positive interaction between the intracellular domain of Slitrk2 and a scaffolding protein involved in protein trafficking. Both Slitrk2 and this potential binding partner are psychiatric risk factors important for synapse function. In this study, we used yeast and mammalian cell models to confirm and map the interaction of Slitrk2 and its potential binding partner. We exogenously overexpressed these proteins in human embryonic kidney (HEK) cells and, with the use of co-immunoprecipitation experiments, we investigated any possible interaction. Additionally, we mapped the specific binding site by using mutated forms of Slitrk2 in a yeast two-hybrid system. Future studies will examine the functional significance of this interaction in synapse formation. Confirming an intracellular binding partner for Slitrk2 allows us to better understand the cellular mechanisms of brain development.
Baqai, Usman M., "Identifying an Intracellular Binding Partner for the Synaptic Adhesion Protein Slitrk2" (2017). Biology Honors Papers. 17.
This research was funded by the Ursinus College Biology Department, Van Sant Funds, the NSF RUI grant 1049768, and the Charles E. Kaufaman New Investigator Award from The Pittsburgh Foundation.