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UBC Theses and Dissertations

Role of class 5 semaphorins in LTD-mediated synapse elimination Gomm, Rachel


The semaphorins are a large protein family, highly conserved across diverse phyla. They are expressed throughout the body, with a diversity of functions including axon guidance, synapse development and plasticity, cell proliferation and migration, dendritic arborization, and neuronal polarization. Class 5 semaphorins, Sema5A and Sema5B, are highly similar transmembrane proteins, functioning in developmental axon guidance and synapse plasticity. Sema5A is genetically-linked to Autism Spectrum Disorder (ASD) and its expression is decreased in people with ASD. However, its function in synapse plasticity is poorly understood. Our study examines the role of Sema5A in synapse elimination and the regulation of class 5 semaphorins by neural activity, specifically long-term potentiation (LTP) and long-term depression (LTD). We demonstrate that Sema5A, like Sema5B mediates synapse elimination of hippocampal neurons. Furthermore, we show that the expression of both class 5 semaphorins is up-regulated by LTD and that LTD enhances the membrane localization of Sema5A. As LTD and Sema5A were independently found to mediate synapse elimination and as we determined that Sema5A is up-regulated by LTD, we tested the hypothesis that LTD-mediates synapse elimination through Sema5A up-regulation. However, we discovered that Sema5A is not required for LTD-mediated synapse elimination and therefore likely functions to eliminate synapses through a separate pathway.

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