Molecular Characterization of a Membrane-Associated Cytoskeletal Motor Family

Abstract

Many large morphological changes in the plasma and intracellular membranes are powered by the actions of cytoskeletal motors. These motors include myosin-Is, which are the widely expressed members of the myosin superfamily that bind directly to membranes, linking them to the actin cytoskeleton. To better understand the molecular roles of myosin-I isoforms, and the mechanisms by which they modulate membrane dynamics, we performed a range of single-molecule biophysical, structural, biochemical, and cell biological experiments to determine force-generating, membrane-binding, and motile properties of these motors. We discovered that there is remarkable diversity among myosin-I isoforms in their ability to alter their ATPase activities in response to mechanical forces, and we are learning how structural features within the motor domain lead to chemomechanical tuning. We have also learned much about the biophysics of the attachment of myosin-I to membrane bilayers in the presence and absence of mechanical load. Our understanding of the biophysical properties of myosin-I isoforms has allowed us to further explore their roles in membrane dynamics via multi-motor in vitro assays that reconstitute membrane motility and tubulation. This work is supported by grants from NIH/NIGMS (GM057247 and GM087253).