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Title: Novel insights into the cellular roles of p600
Author: Parsons, Kari
Advisor: Nguyen, Minh Dang
Keywords: Neuroscience
Issue Date: 21-May-2014
Abstract: p600 is a large multifunctional protein with important roles in protein degradation, cell adhesion, migration and survival. In the central nervous system (CNS), p600 impacts neurogenesis, neuronal migration, and neuronal survival through interactions with microtubules and calmodulin. The C-terminus of p600 containing the microtubule-binding domains interacts with Ndel1 in vitro and in cultured cells. In the developing neocortex, Ndel1, together with Lis1 and the motor Dynein, regulates mitotic spindle orientation in apical progenitors in a manner reminiscent of p600. My thesis investigates the significance of the p600/Ndel1 interaction. I demonstrate an in vivo association between Ndel1 and p600 in brain tissue. In mitotic cells, I found that overexpression of a NDEL1-binding p600 fragment alters NDEL1's subcellular distribution as well as NDEL1/LIS1 ratios critical in Dynein localization. Finally, I report p600 expression in apical progenitors. My work provides mechanistic insight into the cellular roles of p600, including the function of p600 in neurogenesis.
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