NOMENCLATURE CONFLICT NOTE

MYO2 encodes an essential class V myosin heavy chain and MYO4 encodes a second, non-essential, class V myosin (6, 1, 7, 8). 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 (9, 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 (9, 10). 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 (9).

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 (9). C-terminal to the motor domain is a neck region that contains six IQ motifs that can bind calmodulin encoded by CMD1 (9, 11). Myosins are typically regulated by interactions with light chains. The myosin light chain encoded by MLC1 physically interacts with, and regulates Myo2p (12). The binding of the Myo2p tail by the kinesin-like protein Smy1p promotes the polarized localization of Myo2p and impacts Myo2p function (13, 10, 14, 15). While the light chain(s) that regulate Myo4p are yet to be defined, a novel motor-binding protein, She4p, may modulate Myo4p function (16). Myo2p is phosphorylated in vivo and the functional consequences of these modifications are complex (17).

Myo4p is required for the proper regulation of mating-type switching through its role in transporting ASH1 mRNA to the tip of the bud (3, 18, 19, 20). More recent studies indicate that Myo4p has a general role in transporting mRNAs to the bud-tip (21, 22). mRNAs associate with Myo4p via the She2p and She3p proteins. She3p is an adaptor protein that links Myo4p to its cargo. She2p binds to ASH1 and IST2 mRNAs, while She3p binds to both She2p and Myo4p (23, 24, 21). The ribonucleoprotein complexes are thought to translocate to the bud cortex along actin cables because perturbing actin cables with mutants or drugs disrupts the localization of ASH1 and IST2 mRNAs to the bud (19, 20, and 25).

Myo4p also plays a role in efficient inheritance of the cortical endoplasmic reticulum. She3p, but not She2p, is also required for this process suggesting that Myo4 interacts with its cargos through distinct adapter proteins (26).

Last updated: 2006-10-17