Research & Publications
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.