James A. Spudich Ph.D.
We use a multifaceted approach to unravel the mechanism by which molecular motors transduce the chemical energy of ATP hydrolysis into mechanical motion. Work in my laboratory has focused on the myosin family of molecular motors, enzymes that generate the force and motions that underlie muscle contraction, cytokinesis in nonmuscle cells, cell movement, and membrane translocations in cells.We have established both in vitro motility assays and a cell system for functional and molecular genetic analyses of myosin. Using the cellular slime mold Dictyostelium, we provided genetic proof that myosin is required for cytokinesis of cells in suspension, changes in cell shape during morphogenesis, and capping of cell surface receptors. We also designed and developed in vitro assays for ATP-dependent movement of purified myosin on filaments reconstituted from purified actin. This assay has been extended to the single molecule level, using a variety of biophysical approaches. We are measuring directly the interaction of single myosin molecules with single actin filaments, examining both conventional myosin (myosin-II), found in muscle and in the contractile ring of dividing cells, and unconventional myosins such as myosin-V and myosin-VI (in collaboration with Drs. Mark Mooseker, Richard Cheney, and Lee Sweeney), found in nerve cells and other cells where membrane translocations are required.
EducationPh.D., Stanford, 1968
Important ArticlesRobinson, D.N. and Spudich, J.A. (2004). Mechanics and Regulation of Cytokinesis. Current Opinion in Cell Biology 16: 1-7.
Altman, D., Sweeney, H.L., and Spudich, J.A. (2004). The Mechanism of Myosin VI Translocation and Its Load-Induced Anchoring. Cell 116: 737-749.
Ökten, Z., Churchman, L.S., Rock, R.S., and Spudich, J.A. (2004). Myosin VI Walks Hand-Over-Hand along Actin. Nature Struct Mol Biol. 11: 884-887.
Hostetter, D., Rice, S., Dean, S., Altman, D., McMahon, P.M., Sutton, S., Tripathy, A., and Spudich, J.A. (2004). Dictyostelium Myosin Bipolar Thick Filament Formation: Importance of Charge and Specific Domains of the Myosin Rod. PLoS Biol. 2: 1880-1892.
Spudich, J.A. (2004). Two Important Polymers Cross Paths. Proc Natl Acad Sci USA 101:15825-15826
Lakshmikanth, G.S., Warrick, H.M., and Spudich, J.A. (2004). A Mitotic Kinesin-like Protein Required for Normal Karyokinesis, Myosin Localization to the Furrow, and Cytokinesis in Dictyostelium. Proc Natl Acad Sci USA 101: 16519-16524.
Churchman, L.S., Ökten, Z., Rock, R.S., Dawson, J.F., and Spudich, J.A. (2005). Single molecule high-resolution colocalization of Cy3 and Cy5 attached to macromolecules measures intramolecular distances through time. Proc Natl Acad Sci USA 102: 1419-1423.
Rock, R.S., Ramamurthy,B., Dunn,A.R., Beccafico,S., Rami, B.R., Morris,C., Spink,B.J., Franzini-Armstrong,C., Spudich, J.A., and H. Lee Sweeney, H.L. (2005). A Flexible Domain is Essential for the Large Step Size and Processivity of Myosin VI. Molecular Cell 17: 603-609.
Dean, S.O., Rogers, S.L., Stuurman, N., Vale, R.D. and Spudich, J.A. (2005). Distinct pathways control recruitment and maintenance of myosin II at the cleavage furrow during cytokinesis. Proc Natl Acad Sci U S A 102:13473-13478.
Purcell, T.J., Sweeney, H. L. and Spudich, J.A. (2005). A force-dependent state controls the coordination of processive myosin V. Proc Natl Acad Sci U S A 102:13873-13878.
Altman, D., Goswami, D., Spink, B., Hasson, T., Spudich, J.A. and Mayor, S. (2005). Myosin VI is an oligomer on endocytic vesicles in vivo.Submitted.
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