Non-muscle cells also express a large family of other myosin proteins, which have diverse structures and functions in the cell. Following the discovery of conventional muscle myosin, a second member of the family was found in the freshwater amoeba Acanthamoeba castellanii. This protein had a different tail structure and seemed to function as a monomer, and so it was named myosin I (for one-headed). Conventional muscle myosin was renamed myosin II (for two-headed). Subsequently, many other myosin types were discovered. The heavy chains generally start with a recognizable myosin motor domain at the N-terminus and then diverge widely with a variety of C-terminal tail domains (Figure 16–40). The myosin family includes a number of one-headed and two-headed varieties that are about equally related to myosin I and myosin II, and the nomenclature now reflects their approximate order of discovery (myosin III through at least myosin XVIII). Sequence comparisons among diverse eukaryotes indicate that there are at least 37 distinct myosin families in the superfamily. All of the myosins except one move toward the plus end of an actin filament, although they do so at different speeds. The exception is myosin VI, which moves toward the minus end. The myosin tails (and the tails of motor proteins generally) have apparently diversified during evolution to permit the proteins to bind other subunits and to interact with different cargoes.
Some myosins are found only in plants, and some are found only in vertebrates. Most, however, are found in all eukaryotes, suggesting that myosins arose early in eukaryotic evolution. The human genome includes about 40 myosin genes. Nine of the human myosins are expressed primarily or exclusively in the hair cells of the inner ear, and mutations in five of them are known to cause hereditary deafness. These extremely specialized myosins are important for the construction and function of the complex and beautiful bundles of actin found in stereocilia that project from the apical surface of these cells (see Figure 9–51); these cellular protrusions tilt in response to sound and convert sound waves into electrical signals.
The functions of most of the myosins remain to be determined, but several are well characterized. The myosin I proteins often contain either a second actin-binding site or a membrane-binding site in their tails, and they are generally involved in intracellular organization—including the protrusion of actin-rich structures at the cell surface, such as microvilli (see Panel 16–1 and Figure 16–4), and endocytosis. Myosin V is a two-headed myosin with a large step size (Figure 16–41A) and is involved in organelle transport along actin filaments. In contrast to myosin II motors, which work in ensembles and are attached only transiently to actin filaments so as not to interfere with one another, myosin V moves continuously,
Figure 16–40 Myosin superfamily members. Comparison of the domain structure of the heavy chains of some myosin types. All myosins share similar motor domains (shown in dark green), but their C-terminal tails (light green) and N-terminal extensions (light blue) are very diverse. On the right are depictions of the molecular structure for these family members. Many myosins form dimers, with two motor domains per molecule, but a few (such as I, III, and XIV) seem to function as monomers, with just one motor domain. Myosin VI, despite its overall structural similarity to other family members, is unique in moving toward the minus end (instead of the plus end) of an actin filament. The small insertion within its motor head domain, not found in other myosins, is probably responsible for this change in direction.