MYO2 encodes an essential class V myosin heavy chain and MYO4 encodes a second, non-essential, class V myosin (6, 7, 8, 9). Class V myosins are usually homodimers and function as molecular motors that in yeast transport distinct sets of cargo to polarized regions of the cell along actin cables (10, 4). Myo2p predominantly transports membrane-bound organelles, whereas Myo4p moves mRNAs (see below and MYO4). Through evolution Myo4p has lost features found in Myo2p and animal myosins, such as portions of the tail region required for the transport of membrane-bound organelles (10, 11). Still, Myo2p and Myo4p are more closely related to each other than any other myosin. Non-yeast homologs of MYO2 and MYO4 include the mouse dilute gene, chick brain M5a, and the human MYO5A (OMIM), which is mutant in some patients with Griscelli syndrome (10).

Class V myosins have a particular domain architecture and distinct modes of regulation. Myo2p and Myo4p have an N-teminal actin-binding motor domain and a globular C-terminal tail domain separated by a coiled-coil dimerization domain (10). C-terminal to the motor domain is a neck region that contains six IQ motifs that can bind calmodulin encoded by CMD1 (10, 12). Myosins are typically regulated by interactions with light chains. The myosin light chain encoded by MLC1 physically interacts with, and regulates Myo2p (13). The binding of the Myo2p tail by the kinesin-like protein Smy1p promotes the polarized localization of Myo2p and impacts Myo2p function (14, 11, 15, 16). While the light chain(s) that regulate Myo4p are yet to be defined, a novel motor-binding protein, She4p, may modulate Myo4p function (17). Myo2p is phosphorylated in vivo and the functional consequences of these modifications are complex (18).

Myo2p promotes polarized growth by mediating the vectorial transport of organelles along actin cables to sites such as the growing bud during vegetative growth (4), the bud neck during cytokinesis (19), and the shmoo tip during mating (20, 21, 22). Organelles transported into the growing bud include secretory vesicles (6, 23, 24, 11, 25), vacuoles (26), peroxisomes (27), and late-Golgi elements (28). Myo2p also participates in orientation of the mitotic spindle early in the cell cycle (22). Cargo-specific myosin receptors act as links between the cargo and the myosin tail. Myosin receptors include Vac8p-Vac17p on vacuoles (29) and Inp2p on peroxisomes (30). Sec4p, a vesicle-bound rab, associates with Myo2p, and along with Sec2p and Smy1p, is critical for vesicle transport (4). Myo2p participates in spindle orientation by actively transporting Kar9p/Bim1p-decorated microtubule ends into the bud (4). The role of type V myosins in mitochondrial inheritance has been controversial. There is no dispute that actin is required for this process. Early studies suggested that type V myosins are dispensible for this process (31) and demonstrated that the force used for directed mitochondrial movement is generated by Arp2/3-dependent actin nucleation (32). Others have suggested that Myo2p is involved in mitochondrial inheritance (33, 34). A more recent study attempts to reconcile the differences and provides evidence that Myo2p and the rab Ypt11p are required for the retention of newly inherited mitochondria in the bud (35).

Last updated: 2006-10-30