Microtubule (MT) properties vary within seemingly uniform MT network, and MTs with similar properties comprise functionally specialized subsets. In the current funding period, we have characterized a distinct MT subset that nucleates at the Golgi membrane (Golgi-derived MTs). In contrast to the radially organized centrosomal MTs, Golgi-derived MT array is intrinsically asymmetric and is essential for polarity of motile cells. Our previous and preliminary data indicate that Golgi-derived MTs bear unique functions. Being closely associated with the Golgi membrane, these MTs are indispensable for Golgi complex assembly, maintenance and positioning. Despite the obvious essential nature of the maintenance and reorganization of the Golgi in the life cycle and basic behavior of all cells, there is a poor understanding of the intracellular architectural mechanisms that orchestrate its dynamic, temporally regulated functions. Major gaps addressed by our study include: how vesicles are tracked to/from the Golgi, how stack alignment is ensured during Golgi complex assembly, and how they are timely relocated at mitotic onset. Our preliminary and published data indicate that Golgi-derived MTs act as the architectural basis of these precisely coordinated processes. We hypothesize that distinct location of Golgi-derived MTs with their minus ends at the Golgi membrane and their specific association with a MT-binding protein CLASP, which differentially regulates distinct molecular motors, underlies functional specificity of this MT subset. The goal of this proposal is to determine the spatial and molecular mechanisms underlying the unique functions of Golgi-derived MTs. The proposal thus targets a high- impact, fundamental area of mechanistic cell biology.
Our specific aims are: 1. Test whether vesicle delivery driven by Golgi-derived MTs is critical for Golgi homeostasis 2. Determine whether Golgi repositioning prior to cell division is accomplished by Golgi-derived MTs 3. Determine the mechanism whereby Golgi-derived MTs support efficient Golgi stack fusion
A microtubule subset that nucleates at the Golgi membrane is indispensable for Golgi complex assembly, maintenance and positioning. In this project, we propose to determine the spatial and molecular mechanisms underlying the unique functions of Golgi-derived MTs.
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|Arnette, Christopher; Efimova, Nadia; Zhu, Xiaodong et al. (2014) Microtubule segment stabilization by RASSF1A is required for proper microtubule dynamics and Golgi integrity. Mol Biol Cell 25:800-10|
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|Zhu, Xiaodong; Kaverina, Irina (2011) Quantification of asymmetric microtubule nucleation at subcellular structures. Methods Mol Biol 777:235-44|
|Zhu, Xiaodong; Wang, Junxia; Moriguchi, Kazuki et al. (2011) Proper regulation of Cdc42 activity is required for tight actin concentration at the equator during cytokinesis in adherent mammalian cells. Exp Cell Res 317:2384-9|
|Sung, Bong Hwan; Zhu, Xiaodong; Kaverina, Irina et al. (2011) Cortactin controls cell motility and lamellipodial dynamics by regulating ECM secretion. Curr Biol 21:1460-9|
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