Submission Date

4-30-2021

Document Type

Paper- Restricted to Campus Access

Department

Biology

Adviser

Jennifer Round

Committee Member

Simara Price Telesford

Committee Member

Nicole Ivaska

Department Chair

Rebecca Lyczak

Project Description

Synapses are small gaps between neurons that allow communication through the release of neurotransmitters. When synaptic proteins are mis-expressed or mutated, changes in neurodevelopmental disorders and neuropsychiatric diseases can occur. Slitrk2 is one of many synaptic adhesion proteins that induce synapse formation during nervous system development. While the trans-synaptic binding partners of Slitrk2 have been identified, a full understanding of the intracellular signaling mechanisms that traffic and cluster Slitrk2 at synaptic sites are not well understood. Our lab recently found that the scaffold protein PSD-95 is an intracellular binding partner of Slitrk2 (Loomis, Stephens, et al. 2020). This honors project summarizes my contributions to our investigation of the PSD-95/Slitrk2 interaction over the past 3 years. First, we show that PSD-95 clusters Slitrk2 in non-neuronal cells. Second, I show preliminary data suggesting that Slitrk2 colocalizes with PSD-95 in cultured neurons. Third, I describe my attempts to co-immunoprecipitate PSD-95 and Slitrk2 from non-neuronal 293T cells. Confirming this interaction in 293T cells will allow us to mutate a phosphorylation site in Slitrk2 and see if phosphorylation plays a role in PSD-95 binding. Characterizing the protein interactions that drive synapse formation allows us to gain a better understanding of the cellular mechanisms of nervous system development and neuropsychiatric disorders.

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