| Summary: | 碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 99 === Coronins are highly conserved actin-binding proteins in various species. Coronin1B is classified as the type I Coronins. Research has indicated that Coronin1B binds to filamentous actin and Arp2/3 complex, and is involved in regulating several actin-dependent physiological processes by inhibit Arp2/3 nucleating activity. Unlike other Coronin family members, Coronin1B was found ubiquitously expressed in most tissues. Although the actual physiological function of Coronin1B is unclear, its ubiquitous expression profile has indicated that it may play role in actin organization in many cell types. In addition, Di Giovanni et al. identified that Coronin1B was up-regulated by p53 following spinal cord injury in rats. This regulation mechanism is also required for maximal neurite outgrowth in several neuronal cell-lines. To further explore the biological functions of Coronin1B in vivo, the spatial/temporal expression profile of Coronin1B was performed and the phenotypes of the Coronin1B conventional knockout mice, which were previous generated in our laboratory, were analyzed. My project is devoted to study the biological functions of Coronin1B specifically in the nervous system. As a result, Coronin1B was found to be highly expressed in the developing nervous system and maintained highly expressed in the adult olfactory bulb glomerular layer, cerebellum molecular cell layer, and Purkinje cell layer. Surprising, though it play an important role in regulating actin dynamics, the Coro1b null mice were healthily born and showed no obvious phenotype. Further characterization found that loss of Coronin1B caused increased Purkinje cell dendrite length and width in cerebellum. Using rotarod behavior test, we found better motor performance in Coro1b null males compared to littermate controls. In contrast, Coro1b null females exhibited poor motor performance compared to the controls. Further work to characterize these defects in Coro1b null mutants is needed. Finally, western blot analysis confirmed that p53 can partially regulate the Coronin1B expression in the brain cortex, hippocampus and thalamus using p53 knockout mice as the model. Taken together, the function and modulation of Coronin1B in nervous system remain to be elucidated.
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