The goals of these studies are to determine the structure and function of intermediate filaments and their associated proteins in mammalian cells. Intermediate filaments are major cytoskeletal structures and their constituent proteins vary in a cell type specific fashion.
The specific aims of the proposed research are to determine the mechanisms underlying the assembly of intermediate filament networks, the interactions of intermediate filaments with microtubules, and the regulation of their dynamic and motile properties. The techniques employed in these studies include light and electron microscopy, single cell microinjection methods, biochemical characterization of proteins, and the cloning and transfection of wild type and mutant cDNAs in cultured mammalian cells. The results of these studies are related to human health as it has been demonstrated that there are many diseases linked to mutations in the structural proteins comprising intermediate filaments and there are other diseases in which abnormal accumulations of intermediate filaments are a pathological hallmark of disease. The latter include the formation of Mallory bodies in alcoholic liver disease and Lewy bodies in Parkinson's disease.
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| Ralat, Luis A; Kalas, Vasilios; Zheng, Zhongzhou et al. (2011) Ubiquitin is a novel substrate for human insulin-degrading enzyme. J Mol Biol 406:454-66 |
| Nekrasova, Oxana E; Mendez, Melissa G; Chernoivanenko, Ivan S et al. (2011) Vimentin intermediate filaments modulate the motility of mitochondria. Mol Biol Cell 22:2282-9 |
| Mendez, Melissa G; Kojima, Shin-Ichiro; Goldman, Robert D (2010) Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J 24:1838-51 |
| Flitney, Eric W; Kuczmarski, Edward R; Adam, Stephen A et al. (2009) Insights into the mechanical properties of epithelial cells: the effects of shear stress on the assembly and remodeling of keratin intermediate filaments. FASEB J 23:2110-9 |
| Jaitovich, Ariel; Mehta, Semil; Na, Ni et al. (2008) Ubiquitin-proteasome-mediated degradation of keratin intermediate filaments in mechanically stimulated A549 cells. J Biol Chem 283:25348-55 |
| Sivaramakrishnan, Sivaraj; DeGiulio, James V; Lorand, Laszlo et al. (2008) Micromechanical properties of keratin intermediate filament networks. Proc Natl Acad Sci U S A 105:889-94 |
| Goldman, Robert D; Grin, Boris; Mendez, Melissa G et al. (2008) Intermediate filaments: versatile building blocks of cell structure. Curr Opin Cell Biol 20:28-34 |
| Chang, Lynne; Shav-Tal, Yaron; Trcek, Tatjana et al. (2006) Assembling an intermediate filament network by dynamic cotranslation. J Cell Biol 172:747-58 |
| Helfand, Brian T; Chou, Ying-Hao; Shumaker, Dale K et al. (2005) Intermediate filament proteins participate in signal transduction. Trends Cell Biol 15:568-70 |
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