Unconventional myosins, the basis for deafness in mouse and man.

Myosins are molecular motors that use the energy from ATP hydrolysis to generate force and move along actin filaments. Conventional myosin, or myosin-II, has the specialized ability to form bipolar filaments and is the basis for muscle contraction. Mutations in conventional myosins have been observed in man; dominant cardiomyopathies arise from mutations in P-cardiac myosin-II and other myosin-associated structural proteins (reviewed in Vikstrom and Leinwand 1996). Unlike myosin-II, unconventional myosins do not form bipolar filaments. Instead, these novel myosins serve in intracellular movements along actin filaments, primarily within nonmuscle cells. What the specific roles may be, however, has remained elusive. As described by Adato et al. (1997) in this issue of the Journal, as well as by other groups (Weil et al. 1995; Weston et al. 1996; Levy et al. 1997), mutations in one unconventional myosin, myosin-VIIa, lead to Usher disease, a syndromic recessive deafness. Mutations in myosin-VIIa can also lead to nonsyndromic recessive deafness in humans (Liu et al. 1997b; Weil et al. 1997) and result in deafness in the shaker-1 mutant mouse (Gibson et al. 1995). MyosinVIIa is not the only unconventional myosin that is the basis for deafness phenotypes. The gene for mouse myosin-VI encodes the deafness gene, Snell's waltzer (Avraham et al. 1995).