Submission Date

7-26-2016

Document Type

Paper- Restricted to Campus Access

Department

Biology

Second Department

Neuroscience

Faculty Mentor

Jennifer Round

Comments

Presented during the 18th Annual Summer Fellows Symposium, July 22, 2016 at Ursinus College.

Supported by a Charles E. Kaufman New Investigator Award from The Pittsburgh Foundation.

Project Description

Most human brain development occurs during embryonic stages, where neurons use membrane proteins to wire the brain with extreme precision. 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’s syndrome. Slitrk2 specifically has a large intracellular domain with no studied function. Previous preliminary tests investigating potential binding partners have yielded positive interaction between the intracellular domain of Slitrk2 and a scaffolding protein involved in protein trafficking. Slitrk2 and this potential binding partner are both psychiatric risk factors known to be important for synapse structure. In this study we use an array of models to confirm and map the interaction of Slitrk2 and its potential binding partner. We transfected HEK mammalian cells with fluorescent tagged fusion proteins to investigate any possible binding. We also investigated the binding between Slitrk2 and the scaffolding protein in vivo using synaptosomal preps. We conducted western blots to detect the presence of both proteins to later conduct co-immunoprecipitation experiments. Additionally, we mapped the specific binding site 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.

Previous Versions

Jul 26 2016 (withdrawn)

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