Class V myosins

IntroductionThe myosin family of actin-based molecular mo-tors consists of 15 known classes that are structurallydistinct based on comparisons of the primary struc-ture of the motor domains of the known myosinheavy chain genes [1^3]. Information regarding thefunction and/or biochemical properties of most ofthese myosin classes is sparse relative to the well-characterized class II and class I myosins; neverthe-less, the range of proposed functions for these myo-sins is already remarkably broad [1]. There are anumber of recent reviews that provide an overviewof the rapidly growing myosin gene family [1,4^8].Among the best characterized and functionally di-verse of the recently discovered myosin classes arethe class V myosins, the focus of this review (forother reviews see [9^11]).Myosin-V was initially characterized as an unusualcalmodulin binding protein from brain with a num-ber of myosin-like biochemical properties [12^14].Subsequently, myosin-V heavy chain genes werecloned from mouse, yeast and chicken, thus de¢ningthe ¢fth class of actin-based motors [15^19]. Studiesof the mouse and yeast class V myosins provided the¢rst insights regarding the cellular function of myo-sin-V. Phenotypes of the mutant dilute mouse andthe temperature-sensitive yeast mutant, myo2-66 ledto the hypothesis that class V myosins may functionin cell polarity and membrane tra⁄cking [15,16].Moreover, mutations in the human ortholog of thedilute heavy chain gene cause Griscelli syndrome, arare recessive disease characterized by pigmentarydilution and in most, but not all cases immunode¢-ciency [20^22]. Neurological disorders have also beenreported in Griscelli syndrome patients [22,23]. Sincethese ¢rst studies, a great deal has been learnedabout the biochemistry, biophysics and cellular func-tion of the class V myosins. This review will discussthe emerging evidence that myosin-V is a processiveactin-based motor that has multiple functions in thecell ranging from mRNA transport, cell polarity andmembrane tra⁄cking.There are currently nine complete myosin-V heavychain sequences known (Fig. 1). Analysis of the twocompleted eukaryotic genomes of Saccharomyces ce-revisiae and Caenorhabditis elegans reveals that yeasthave two class V myosins, while C. elegans has asingle class V myosin heavy chain gene. In verte-brates, there are at least three distinct subclasses ofmyosin-V. The three most closely related heavy chainsequences, that of chicken brain myosin-V, the