Presenter: Erik Burlingame
Faculty Mentor: Philip Washbourne
Presentation Type: Poster 50
Primary Research Area: Science
Major: Biochemistry
Funding Source: Undergraduate Research Fellowship, Center on Teaching and Learning, $9369; UROP Mini-grant, Undergraduate Research Opportunity Program, $1000; McNair Scholars Program, TRiO, $13221; Swayne Family Scholarship, Swayne Family Foundation, $8800
Synapses are functional units of connectivity that permit the exchange of information between cells in the nervous system. As such, aberrant synapse formation is implicated in a host of neurodevelopmental disorders. Normal formation of synapses requires the transport, recruitment, and stabilization of the synaptic vesicle-regulating protein synapsin to nascent synapses. Recruitment of synapsin to nascent synapses is regulated by cyclin-dependent
kinase 5 (Cdk5), but the downstream effectors of Cdk5 that enable this recruitment remain elusive. Using a zebrafish model, our research examines a putative role of the scaffolding protein calcium/calmodulin-dependent serine kinase a (CASKa) in synapsin recruitment. The mammalian ortholog CASK participates in multipartite transport complexes and is localized to presynaptic terminals by Cdk5-mediated phosphorylation. These observations spurred our hypothesis that Cdk5 phosphorylates CASKa to recruit synapsin to presynaptic terminals. Using a stereotypical touch-evoked behavior to assess synapse function, we found that embryos misexpressing non-phosphorylatable CASK protein exhibit a significant reduction in touch response when compared to embryos expressing either endogenous CASKa or exogenous mammalian CASK protein. Immunofluorescent characterization of synapses from touch-sensitive neurons in these touch-insensitive embryos shows deficits in synapsin localization, further supporting a physical intersection of CASK and Cdk5 during synaptic development. With human CASK dysfunction being linked to defects in synapses, microcephaly, and X-linked intellectual disability, this examination may help establish a novel target for CASK-associated disorder remediation.