Author ORCID Identifier

orcid.org/0000-0001-7432-1729

Defense Date

2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Human Genetics

First Advisor

Rita Shiang

Second Advisor

Xiangning Chen

Abstract

CMYA5 is a candidate gene for schizophrenia because of the association of variant rs10043986 (Pro4063Leu). Studies of CMYA5 and its gene product, myospryn, in brain and neuronal cells have not been previously reported. We examined the neuronal expression of myospryn and its binding partner, desmin intermediate filament (IF), and investigated the difference in binding and colocalization of the two alleles of myospryn to IFs. Myospryn and desmin are expressed in brain regions. Using yeast two-hybrid and surface plasmon resonance, the T allele (Leu) is found to have higher binding affinity to desmin than the C allele (Pro). Myospryn localizes to the cytoplasm and nucleus and is weakly to moderately colocalized with desmin in myoblast, neuroblastoma, and glioblastoma cell lines. Peripherin and vimentin, brain-related IFs, have similar degrees of colocalization. rs10043986 does not affect the colocalization of myospryn to IFs, but it affects the colocalization of myospryn to F-actin Dysbindin, another schizophrenia candidate gene, is found to weakly colocalize with myospryn in myoblast, neuroblastoma, and glioblastoma cell lines. The expression of myospryn in the brain suggests functions that are relevant to schizophrenia. rs10043968 is a functional variant that results in differential binding of myospryn to desmin. We hypothesize that the interaction between myospryn to IFs provides structural support and efficient rearrangement of the cytoskeleton network during early neuritogenesis. Myospryn might also be involved in intracellular trafficking affecting synaptic function through dysbindin in conjunction with the BLOC-1 complex and IFs. Myospryn might also play important roles in neurotransmission based on a literature search of its binding partners PKA, calcineurin, and α-actinin.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-11-2017

Available for download on Friday, May 11, 2018

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