The work described in this project is aimed at determining the structure, properties, and functions of intermediate filaments (IF) in mammalian cells. Many of the experiments take advantage of recently discovered properties of IF showing that they are dynamic cytoskeletal proteins. Dr. Goldman proposes to use specific peptides designed to disrupt IF assemblies in vivo using microinjection methods and to determine the physiological changes which accompany their disassembly. He also proposes to study the mechanisms by which phosphorylation modifies IF organization in cells using a variety of cellular and molecular approaches, including microscopic, biochemical, and immunological techniques. Another major goal is to determine the function of one of the major IF associated proteins, IFAP300. This protein appears to be involved in regulating the distribution and supramolecular organization of IF networks in cells via its crossbridging function. IFAP300 also appears to be involved in interactions with other cytoskeletal systems such as microtubules. In order to further understanding of the function of this protein, it is being cloned and sequenced using standard methods.
| Goldman, Robert D; Cleland, Megan M; Murthy, S N Prasanna et al. (2012) Inroads into the structure and function of intermediate filament networks. J Struct Biol 177:14-23 |
| Helfand, Brian T; Mendez, Melissa G; Murthy, S N Prasanna et al. (2011) Vimentin organization modulates the formation of lamellipodia. Mol Biol Cell 22:1274-89 |
| 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 |
| 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 |
| 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 |
| Helfand, Brian T; Mendez, Melissa G; Pugh, Jason et al. (2003) A role for intermediate filaments in determining and maintaining the shape of nerve cells. Mol Biol Cell 14:5069-81 |
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