Myosin VI: Roles for a Minus End-directed Actin Motor in Cells

The recent discovery that the class VI myosin is minus end-directed (Schliwa, 1999; Wells et al., 1999) allows new mechanisms of actin-based motility to exist in cells. This will prompt reexamination of a broad range of cell movements previously difficult to explain by conventional force generating mechanisms. Myosins are a large family of molecular motor proteins divided into 15 or more classes, and are the only known type of actin-based motor. Intrinsically, an individual myosin converts energy derived from ATP hydrolysis into unidirectional movement towards only one specified end of an actin filament: either the plus (barbed-) or minus (pointed-) end. Minus end directionality in myosin VI is unique: all other myosins tested are plus end-directed actin motors. Myosin VI plays a key role in cell motility and shape change events in many animal species (Table I), and is essential for hearing in mice (Avraham et al., 1995) and fertility in flies (Hicks et al., 1999). This review discusses two plausible basic molecular functions for a minus end-directed actin motor in a cell: transportation of cargo, an expected role for an actin motor; and generation of cell expansion force, a new theory. I then speculate how cargo transport and cell expansion force participate in three distinct shape change events in which myosin VI activity is important.