Irina Kaverina, Ph.D.
Associate Professor of Cell and Developmental Biology
Vanderbilt University Medical Center
465 21st Ave So, U-4213A Learned Lab
Nashville, TN 37232-8240
Functions and Regulation of Microtubules
Architecture of a eukaryotic cell largely depends on microtubules (MTs), 25-nm self-assembling polymers that serve as highways for organelle and molecular transport within a cell. During cell division, MTs drive chromosome segregation. In interphase cells, MTs position organelles and site-specific activities like actin assembly or proteolysis, thereby defining cell shape and polarity. For years, an intriguing question has been how MTs within a cell can perform multiple actions that are spatially and temporally distinct. We think that it can only be possible if functionally distinct subsets exist within the MT network and if these subsets are precisely localized within a cell.
Our lab is interested in:
1) Establishing principles of diversity and asymmetry within MT networks. We study the MT network as a combination of subsets of diverse origin, dynamics and molecular composition. We have recently discovered a novel MT population, which forms at Golgi complex and are distinct from the centrosomal MT array. Elucidating their molecular and functional properties is one of our close goals.
2) Understanding how variations in MT subsets are translated into specifics of cellular architecture and functioning. We aim to resolve general principles of this regulatory system as well as its cell-type-specific functions. In particular, we study MT-dependent regulation of: 1) Golgi complex organization and trafficking; 2) invasive podosomes in vascular smooth muscle cells; 3) insulin secretion in pancreatic beta cells.
The astrophysicist Bernard Haisch once said "Advances are made by answering questions. Discoveries are made by questioning answers." This approach is very appealing to us. Our research is based on a set of dogma-challenging hypotheses that we test through a unique combination of cutting edge high-resolution microscopy techniques supported by molecular and biochemical approaches and merged with mathematical modeling.
- Arnette, C, Efimova, N, Zhu, X, Clark, GJ, Kaverina, I Microtubule segment stabilization by RASSF1A is required for proper microtubule dynamics and Golgi integrity. Mol Biol Cell, 25(6), 800-10, 2014.
- Zhu, X, Kaverina, I Golgi as an MTOC: making microtubules for its own good. Histochem Cell Biol, 140(3), 361-7, 2013.
- Maia, AR, Zhu, X, Miller, P, Gu, G, Maiato, H, Kaverina, I Modulation of Golgi-associated microtubule nucleation throughout the cell cycle. Cytoskeleton (Hoboken), 70(1), 32-43, 2013.
- Vinogradova, T, Paul, R, Grimaldi, AD, Loncarek, J, Miller, PM, Yampolsky, D, Magidson, V, Khodjakov, A, Mogilner, A, Kaverina, I Concerted effort of centrosomal and Golgi-derived microtubules is required for proper Golgi complex assembly but not for maintenance. Mol Biol Cell, 23(5), 820-33, 2012.
- Sung, BH, Zhu, X, Kaverina, I, Weaver, AM Cortactin controls cell motility and lamellipodial dynamics by regulating ECM secretion. Curr Biol, 21(17), 1460-9, 2011.
- Kaverina, I, Straube, A Regulation of cell migration by dynamic microtubules. Semin Cell Dev Biol, 22(9), 968-74, 2011.
- Miller, PM, Folkmann, AW, Maia, AR, Efimova, N, Efimov, A, Kaverina, I Golgi-derived CLASP-dependent microtubules control Golgi organization and polarized trafficking in motile cells. Nat Cell Biol, 11(9), 1069-80, 2009.
- Vinogradova, T, Miller, PM, Kaverina, I Microtubule network asymmetry in motile cells: Role of Golgi-derived array. Cell Cycle, 8(14), 2009.
- Efimov, A, Schiefermeier, N, Grigoriev, I, Ohi, R, Brown, MC, Turner, CE, Small, JV, Kaverina, I Paxillin-dependent stimulation of microtubule catastrophes at focal adhesion sites. J Cell Sci, 121(Pt 2), 196-204, 2008.
- Efimov, A, Kharitonov, A, Efimova, N, Loncarek, J, Miller, PM, Andreyeva, N, Gleeson, P, Galjart, N, Maia, AR, McLeod, IX, Yates, JR, Maiato, H, Khodjakov, A, Akhmanova, A, Kaverina, I Asymmetric CLASP-Dependent Nucleation of Noncentrosomal Microtubules at the trans-Golgi Network. Dev Cell, 12(6), 917-30, 2007.
- Rid, R, Schiefermeier, N, Grigoriev, I, Small, JV, Kaverina, I The last but not the least: the origin and significance of trailing adhesions in fibroblastic cells. Cell Motil Cytoskeleton, 61(3), 161-71, 2005.
- Kaverina, I, Krylyshkina, O, Small, JV Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J Cell Biol, 146(5), 1033-44, 1999.
- Kaverina, I, Rottner, K, Small, JV Targeting, capture, and stabilization of microtubules at early focal adhesions. J Cell Biol, 142(1), 181-90, 1998.