UC Davis

The activation of kinesin motors is a complex and finely regulated process governed by a multitude of factors within the cellular environment. This dissertation investigates the intricate interplay of vesicles, adaptor proteins, and microtubule-associated proteins (MAPs) in modulating kinesin motor activity. I explored the functional significance of various adaptor proteins, including Nesprin 2G, SKIP, and the pathogenic protein PipB2, in regulating kinesin-mediated intracellular transport. Our findings elucidate the distinct contributions of these adaptors to kinesin activation, shedding light on their roles in physiological and pathological contexts. Additionally, I investigated the influence of MAPs, particularly Map7, on kinesin activation in the presence of the adaptors, revealing intricate regulatory networks governing motor protein dynamics on microtubules. Furthermore, we initiated the development of nanodiscs as a novel tool to mimic lipid environments in vitro, particularly for total internal reflection fluorescence (TIRF) microscopy studies. This innovative approach provides a platform for dissecting the impact of lipid composition on kinesin activation and transport dynamics. Collectively, our research advances our understanding of the complex regulation of kinesin motor activation, offering insights into fundamental cellular processes and potential therapeutic avenues for diseases associated with dysregulated intracellular transport.