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Richard
E. Cheney, PhD Education:
Motor Proteins, Cytoskeleton, and Cell Motility Our research
centers on determining the properties and roles of molecular motors. In
the past several years it has become apparent that the myosin superfamily
of actin-based motor proteins is much larger and far more diverse than
previously realized, and in a recent genome based analysis we predicted
8 previously unrecognized myosin genes. Although the conventional
myosins responsible for processes such as muscle contraction and cell
division have been intensively studied for almost half a century, very
little is known about the unconventional myosins. We are particularly
interested in the cell and molecular biology of the unconventional myosins,
since these molecules are hypothesized to underlie cellular phenomena
ranging from organelle transport to signal transduction.
Our long range goals are to determine the molecular basis of processes such as organelle transport, cell crawling, and filopodial dynamics by characterizing the properties and functions of the motor proteins believed to power these movements. Much of our work has focused on brain myosin-V, a major component of brain that appears to power actin-based organelle transport in places such as the dendritic spine; loss of this myosin in mutant mice leads to seizures and death. We have also discovered a new member of the myosin-V family (Myo5c) and have implicated this myosin in the transport of a specific membrane compartment. Given that that Myo5c is a major class V myosin of secretory/epithelial tissues, we suspect that it powers actin-based organelle transport in many of the physiologically critical cells and tissues of the human body. We are also interested in devising improved motility assays that will allow us to reconstitute actin-based organelle transport so as to investigate mechanisms of motor regulation and docking.
We have also begun to characterize myosin-X, a newly discovered myosin that is characterized by the presence of multiple PH (pleckstrin homology) domains. Video microscopy and live cell imaging with GFP constructs indicate that myosin-X exhibits a striking localization to the tips of filopodia. More importantly, we have also discovered that myosin-X undergoes remarkable forward and rearward movements within filopodia and we are thus especially interested in investigating the properties and functions of this novel form of actin-based motility. We are currently investigating the roles of myosin-X in a variety of important processes including PI-3-kinase signaling, phagocytosis, filopodial dynamics, growth cone extension, tumor cell crawling, focal complex formation, and cell-cell signaling.
Recent Publications: Pi X, Ren R, Kelley R, Zhang C, Moser M, Bohil AB, Divito M, Cheney RE and Patterson C. (2007) Sequential Roles for Myosin-X in BMP6-dependent filopodial extension, migration, and activation of BMP receptors. J. Cell Biol. 179:1569-1582. Sigal YJ, Quintero OA, Cheney RE, and Morris AJ. (2007) Cdc42 and ARP2/3-independent regulation of filopodia by an integral membrane lipid-phosphatase-related protein. J. Cell Sci. 120:340-352. Kolesnikova L, Bohil AB, Cheney RE and Becker S. (2007) Budding of Marburg virus is associated with filopodia. Cell. Microbiol. 9:939-951. Bohil AB, Robertson BW, and Cheney RE. (2006) Myosin-X is a molecular motor that functions in filopodia formation. Proc. Natl. Acad. Sci. USA, 103:12411-12416. Sousa AD, Berg JS, Robertson BW, Meeker R and Cheney RE. (2006) Myo10 in brain: developmental regulation, identification of a headless isoform, and dynamics in neurons. J. Cell Sci. 199:184-194. Sousa AD and Cheney RE. (2005) Myosin-X: A Molecular Motor at the Cell's Fingertips. Trends Cell Biol. 15:533-539. Weber KL, Sokac AM, Berg JS, Cheney RE, Bement WM. (2004) A microtubule-binding myosin required for nuclear anchoring and spindle assembly. Nature 431:325-9. Zhang H, Berg JS, Li Z, Wang Y, Lang P, Sousa AD, Bhaskar A, Cheney RE, Stromblad S. (2004) Myosin-X provides a motor-based link between integrins and the cytoskeleton. Nat Cell Biol. 6(6):523-31. Cox D, Berg JS, Cammer M, Chinegwundoh JO, Dale BM, Cheney RE and Greenberg S. (2002) Myosin X is a downstream effector of PI(3)K during phagocytosis. Nature Cell Biology . Rodriguez OC and RE Cheney (2002). Human myosin-Vc is a novel class V myosin expressed in epithelial cells. J. Cell Sci. 115: 991-1004. Berg JS and RE Cheney (2002). Myosin-X is an unconventional myosin that undergoes intrafilopodial motility. Nature Cell Biology 4:246-256. Cheney RE and OR Rodriguez (2001). A switch to regulate the motor. Science 293:1263-1264. Puthalakath H, Villunger A, O'Reilly LA, Beaumont JG, Coultas L, Cheney RE, Huang DC and Strasser A. (2001) Bmf: A Pro-Apototic BH3-only Protein Regulated by Interaction with the Myosin-V Actin Motor Complex, Activated by Anoikis. Science 293:1829-1832. Berg JS,
Powell BC and Cheney RE. (2001) A Millennial Myosin Census. Mol.
Biol. Cell 12:780-794. Reif M, Rock RS, Mooseker MS, Cheney RE and Spudich JA. (2000) Myosin-V Stepping Kinetics: A Molecular Model for Processivity. Proc. Natl. Acad. Sci. USA 97:9482-9486. Mehta AD, Rock RS, Rief M, Spudich JA, Mooseker MS and Cheney RE. (1999) Myosin-V is a Processive Actin-Based Motor. Nature 400:590-593.
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