Irina Kaverina, Ph.D.
Assistant Professor of Cell and Developmental Biology
Vanderbilt University Medical Center
465 21st Ave So, U-4213A Learned Lab
Nashville, TN 37232-8240
Microtubule Network as an Organizer of Cellular Architecture
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 not at the centrosome. Golgi-derived MTs are molecularly and functionally distinct from the centrosomal MT array. Elucidating their regulation and significance is one of our close goals.
2) Understanding how variations in MT subsets are translated into specifics of cellular architecture and functioning. MTs are essential for organization, shape, polarity and motility of various cell types. MT dependence varies between cell types. We aim to resolve general principles of this regulatory system as well as their cell type-specific tuning essential for distinct cellular phenotypes. Our particular interests are MT-dependent motile properties of normal and cancer cells and MT-dependent organization of contractile actin cytoskeleton in vascular smooth muscle 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.
- 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, Kaverina, I Significance of microtubule catastrophes at focal adhesion sites. Cell Adh Migr, 3(3), 2009.
- Broussard, JA, Webb, DJ, Kaverina, I Asymmetric focal adhesion disassembly in motile cells. Curr Opin Cell Biol, 20(1), 85-90, 2008.
- 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.
- Gimona, M, Kaverina, I, Resch, GP, Vignal, E, Burgstaller, G Calponin repeats regulate actin filament stability and formation of podosomes in smooth muscle cells. Mol Biol Cell, 14(6), 2482-91, 2003.
- Small, JV, Kaverina, I Microtubules meet substrate adhesions to arrange cell polarity. Curr Opin Cell Biol, 15(1), 40-7, 2003.
- Krylyshkina, O, Anderson, KI, Kaverina, I, Upmann, I, Manstein, DJ, Small, JV, Toomre, DK Nanometer targeting of microtubules to focal adhesions. J Cell Biol, 161(5), 853-9, 2003.
- Kaverina, I, Stradal, TE, Gimona, M Podosome formation in cultured A7r5 vascular smooth muscle cells requires Arp2/3-dependent de-novo actin polymerization at discrete microdomains. J Cell Sci, 116(Pt 24), 4915-24, 2003.
- Small, JV, Geiger, B, Kaverina, I, Bershadsky, A How do microtubules guide migrating cells. Nat Rev Mol Cell Biol, 3(12), 957-64, 2002.
- Krylyshkina, O, Kaverina, I, Kranewitter, W, Steffen, W, Alonso, MC, Cross, RA, Small, JV Modulation of substrate adhesion dynamics via microtubule targeting requires kinesin-1. J Cell Biol, 156(2), 349-59, 2002.
- Kaverina, I, Krylyshkina, O, Small, JV Regulation of substrate adhesion dynamics during cell motility. Int J Biochem Cell Biol, 34(7), 746-61, 2002.
- Kaverina, I, Krylyshkina, O, Beningo, K, Anderson, K, Wang, YL, Small, JV Tensile stress stimulates microtubule outgrowth in living cells. J Cell Sci, 115(Pt 11), 2283-91, 2002.
- Beningo, KA, Dembo, M, Kaverina, I, Small, JV, Wang, YL Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J Cell Biol, 153(4), 881-8, 2001.
- Kaverina, I, Krylyshkina, O, Gimona, M, Beningo, K, Wang, YL, Small, JV Enforced polarisation and locomotion of fibroblasts lacking microtubules. Curr Biol, 10(12), 739-42, 2000.
- Oliferenko, S, Kaverina, I, Small, JV, Huber, LA Hyaluronic acid (HA) binding to CD44 activates Rac1 and induces lamellipodia outgrowth. J Cell Biol, 148(6), 1159-64, 2000.
- Small, JV, Rottner, K, Kaverina, I Functional design in the actin cytoskeleton. Curr Opin Cell Biol, 11(1), 54-60, 1999.
- 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.
- Kaverina, IN, Minin, AA, Gyoeva, FK, Vasiliev, JM Kinesin-associated transport is involved in the regulation of cell adhesion. Cell Biol Int, 21(4), 229-36, 1997.