Mark S. Mooseker, Ph.D.

Ross Granville Harrison Professor of Molecular, Cellular & Developmental Biology, Cell Biology, and Pathology
Mooseker lab website Phone: (203) 432-3468 Lab: (203) 432-3469 Fax: (203) 432-6161 e-mail: mark.mooseker@yale.edu		Department of Molecular Cellular and Developmental Biology 219 Prospect Street PO Box 208103 New Haven, CT 06520-8103 <Courier Address> 219 Prospect Street, KBT 352 (Lab: KBT 342) New Haven, CT 06511-2106

Molecular underpinnings of cytoskeletal structure, motility and assembly

Our laboratory pursues questions regarding the molecular and functional organization of the cell's cytoskeleton. The major thrust of current effort is focused on the molecular and functional characterization of actin-filament based molecular motors - i. e. myosins. To date, 14 structurally distinct, evolutionarily ancient classes of this molecular motor in addition to the familiar two-headed, filament forming myosins of muscle and nonmuscle cells have been identified (Mermall et al. 1998). In vertebrate cells, multiple myosins of multiple classes are expressed and for most of these myosins little is known regarding their function since most have only just been dis-covered. At present we are conducting studies on a number of the novel myosins identified by our laboratory.

Ongoing projects include the following: a) cell biological and molec-ular genetic assessment of novel myosin functions in selected cell lines, b) l biochemical and biophysical assessment of mechanochemical (motor) properties (e.g. Post et al. 1998); c) characterization of myosin-dependent organelle transport (Evans et al. 1998; Reck-Peterson et al. 1999); d) identification of interacting myosin binding proteins and "reverse-genetic" analysis of myosin function in Drosophila and yeast. Among the myosins recently characterized by our laboratory include three classes of motor (myosins-V, VI, and VII) that are target genes for well characterized mutations in mouse and man (See Hasson et al. 1997; Mermall et al. 1998).

A key hypothesis to be tested is that while some of the myosins expressed in the cell are probably involved in motile phenomena such as organelle movement (e.g. Evans et al. 1998) or endocytosis (e.g. Swanson et al. 1999), others utilize their mechanochemical properties not to locomote but rather to mechano-chemically modulate the biological activities of those proteins with which that motor interacts (e.g. a membrane pump or channel). Still other myosins are likely to be key players in a variety of signal transduction cascades based on the identification of a variety of protein domains (e.g. SH-3, pleckstrin homology, GAP domains) that have been identified within the tail (non-motor) domains of certain myosins (e.g Post et al. 1998).

Recent Publications

Evans, L.L., A.J. Lee, P.C. Bridgman and M.S. Mooseker. 1998. Vesicle associated brain myosin-Va can be activated to catalyze actin-based transport. J. Cell Sci. 111: 2055-2066.

Mermall, V., P.L. Post, and M.S. Mooseker. 1998. Unconventional myosins in cell movement, membrane traffic, and signal transduction. Science. 279:527-533.

Mehta, A.D., R.S. Rock, M. Rief, S.A. Spudich, M.S. Mooseker, and R.E. Cheney. 1999. Myosin-V is a processive actin-based motor. Nature. 400:590-593.

Reck-Peterson, S.L., P.J. Novick, and M.S. Mooseker. 1999. The tail of a yeast class V myosin, myo2p, functions as a localization domain. Mol Biol Cell. 10:1001-17.

Espindola, F.S., D.M. Suter, L.B. Partata, T. Cao, J.S. Wolenski, R.E. Cheney, S.M. King, and M.S. Mooseker. 2000. The light chain composition of chicken brain myosin-Va: calmodulin, myosin-II essential light chains, and 8-kDa dynein light chain/PIN. Cell Motil Cytoskeleton. 47:269-81.

Rief, M., R.S. Rock, A.D. Mehta, M.S. Mooseker, R.E. Cheney, and J.A. Spudich. 2000. Myosin-V stepping kinetics: A molecular model for processivity [In Process Citation]. Proc Natl Acad Sci U S A. 97:9482-6.

Suter, D.M., F.S. Espindola, C.H. Lin, P. Forscher, and M.S. Mooseker. 2000. Localization of unconventional myosins V and VI in neuronal growth cones. J Neurobiol. 42:370-82.

Reck-Peterson, S.L., M.J. Tyska, P.J. Novick, and M.S. Mooseker. 2001. The yeast class V myosins, Myo2p and Myo4p, are nonprocessive actin-based motors. J Cell Biol. 153:1121-6.

Post, P.L., M.J. Tyska, C.B. O'Connell, K. Johung, A. Hayward, and M.S. Mooseker. 2002. Myosin-IXb is a single-headed and processive motor. J Biol Chem. 277:11679-83.

Biemesderfer, D., S.A. Mentone, M. Mooseker, and T. Hasson. 2002. Expression of myosin VI within the early endocytic pathway in adult and developing proximal tubules. Am J Physiol Renal Physiol. 282:F785-94.

O'Connell, C.B., and M.S. Mooseker. 2003. Native Myosin-IXb is a plus-, not a minus-end-directed motor. Nat Cell Biol. 5:171-2.

Tyska, M.J., and M.S. Mooseker. 2004. A role for myosin-1A in the localization of a brush border disaccharidase. J Cell Biol. 165:395-405.

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