Extensive Research Description
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, 24 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. 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 discovered. 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 molecular genetic assessment of novel myosin functions in selected cell lines; b) biochemical and biophysical assessment of mechano-chemical (motor) properties; c) characterization of myosin-dependent organelle transport and membrane traffic; d) phenotypic analysis of myosin mutants in mouse and Drosophila. Among the myosins recently characterized by our laboratory include five classes of motor (myosins-I,V, VI, VII, and IX) that are target genes for well characterized mutations in mouse and man.
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 or endocytosis others utilize their mechanochemical properties not to locomote but rather to mechanochemically 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.
- Krendel M, Kim SV, Willinger T, Wang T, Kashgarian M, Flavell RA, Mooseker MS (2009) Disruption of Myosin 1e promotes podocyte injury. J Am Soc Nephrol 20: 86-94.
- Chang W, Zaarour R F, Mooseker MS (2008) Myo2p, a class V myosin in budding yeast, associates with a large ribonucleic acid-protein complex that contains mRNAs and subunits of the RNA-processing body. RNA 14: 491-502.
- Mooseker, M. S and B. Foth. 2008 The structural and functional diversity of the myosin family of actin-based molecular motors. In Myosins. Edited by L. Coluccio. Springer, NY. pp 1-34
- Hegan, P.S., V. Mermall, L.G. Tilney and M. S. Mooseker. 2007 Roles for Drosophila melanogaster myosin IB in maintenance of enterocyte brush border structure and resistance to the bacterial pathogen, Pseudomonas entomophila Mol. Biol. Cell. 8(11):4625-36
- Holt, J.P, K. Bottomly and M. S. Mooseker. 2007. Assessment of Myosin II, Va,VI and VIIa loss of function on endocytosis and endocytic vesicle motility in bone marrow-derived dendritic cells. Cell Motility Cytoskeleton. 64: 756-766
- Krendel, M., E. Osterweil and M. S. Mooseker.2007 Myosin 1E interacts with synaptojanin-1 and dynamin and is involved in endocytosis. FEBS Lett. 581: 644-650.
- Kim, S.V., W.Z. Mehal, X. Dong, C. Heinrich, M. Dembo, M. S. Mooseker, D. Wu and R. A. Flavell. 2006. Modulation of cell adhesion and motility in the immune system by Myosin If. Science 314:136-9.