Slip sliding away with myosin V
- Laboratory of Cell Biology, Building 50, Room 2523, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
Life is complicated. Things would be much simpler for myosin V if it had to contend only with the in vitro environments created to facilitate elucidation of its mechanochemical properties: isolated actin filament tracks with simple geometries, minimal physical barriers to movement, and no need to interface with microtubule motors that normally cooperate with it (1). But in the cell, myosin V must deal with actin filament networks composed of randomly oriented and/or branched filaments, numerous physical barriers to movement of its vesicular cargo, and the necessity to work in a coordinated fashion with plus-end-directed microtubule motors in a partnership that couples long-range vesicle movement on microtubules with short-range actin-based movement by myosin V in the cell periphery (2, 3). In the paper by Ali et al. in a recent issue of PNAS (4), the authors have begun to tackle this complexity by designing in vitro motility assays in which myosin V encounters either intersecting/branched actin filaments or actin–microtubule intersections. The results are both informative and surprising.
In the first set of experiments, the authors visualized by total internal reflection fluoresence (TIRF) microscopy the movement of a quantum dot-labeled heavy meromyosin (HMM)-like fragment of mouse myosin Va [a dimeric fragment containing the myosin's motor domains but lacking its C-terminal cargo-binding globular tail domains (GTD)] on actin filaments applied to a coverslip by a two-step application, such that the second set of filaments lay at various angles across the top of the first set of filaments. What they observed is that the myosin is perfectly capable of either stepping over an intersecting filament or switching seamlessly to movement on the intersecting filament. Moreover, the myosin can switch filaments that intersect at angles as acute as 150°, suggesting that it is quite flexible, a property that bodes well for its movement …
*To whom correspondence should be addressed. E-mail: hammerj{at}nhlbi.nih.gov
