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.
| Tonucci, Facundo M; Ferretti, Anabela; Almada, Evangelina et al. (2018) Microtubules regulate brush border formation. J Cell Physiol 233:1468-1480 |
| Sanders, Anna A W M; Chang, Kevin; Zhu, Xiaodong et al. (2017) Nonrandom ?-TuNA-dependent spatial pattern of microtubule nucleation at the Golgi. Mol Biol Cell 28:3181-3192 |
| Arnette, Christopher; Frye, Keyada; Kaverina, Irina (2016) Microtubule and Actin Interplay Drive Intracellular c-Src Trafficking. PLoS One 11:e0148996 |
| Zhu, Xiaodong; Efimova, Nadia; Arnette, Christopher et al. (2016) Podosome dynamics and location in vascular smooth muscle cells require CLASP-dependent microtubule bending. Cytoskeleton (Hoboken) 73:300-15 |
| Grimaldi, Ashley D; Zanic, Marija; Kaverina, Irina (2015) Encoding the microtubule structure: Allosteric interactions between the microtubule +TIP complex master regulators and TOG-domain proteins. Cell Cycle 14:1375-8 |
| Sanders, Anna A W M; Kaverina, Irina (2015) Nucleation and Dynamics of Golgi-derived Microtubules. Front Neurosci 9:431 |
| Tonucci, Facundo M; Hidalgo, Florencia; Ferretti, Anabela et al. (2015) Centrosomal AKAP350 and CIP4 act in concert to define the polarized localization of the centrosome and Golgi in migratory cells. J Cell Sci 128:3277-89 |
| Zhu, Xiaodong; Hu, Ruiying; Brissova, Marcela et al. (2015) Microtubules Negatively Regulate Insulin Secretion in Pancreatic ? Cells. Dev Cell 34:656-68 |
| Maki, Takahisa; Grimaldi, Ashley D; Fuchigami, Sotaro et al. (2015) CLASP2 Has Two Distinct TOG Domains That Contribute Differently to Microtubule Dynamics. J Mol Biol 427:2379-95 |
| Cleghorn, Whitney M; Branch, Kevin M; Kook, Seunghyi et al. (2015) Arrestins regulate cell spreading and motility via focal adhesion dynamics. Mol Biol Cell 26:622-35 |
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