or processively, along actin filaments without letting go. Myosin V functions are well studied in the yeast Saccharomyces cerevisiae, which undergoes a stereotypical pattern of growth and division called budding. Actin cables in the mother cell point toward the bud, where actin is found in patches that concentrate where cell wall growth is taking place. Myosin V motors carry a wide range of cargoes— including mRNA, endoplasmic reticulum, and secretory vesicles—along the actin cables and into the bud. In addition, myosin V mediates the correct partitioning of organelles such as peroxisomes and mitochondria between mother and daughter cells (see Figure 16–41B).
Using their neck domain as a lever arm, myosins convert ATP hydrolysis into mechanical work to move along actin filaments in a stepwise fashion. Skeletal muscle is made up of myofibrils containing thousands of sarcomeres assembled from highly ordered arrays of actin and myosin II filaments, together with many accessory proteins. Muscle contraction is stimulated by calcium, which causes the actin-filament-associated protein tropomyosin to move, uncovering myosin binding sites and allowing the filaments to slide past one another. Smooth muscle and non-muscle cells have less well-ordered contractile bundles of actin and myosin, which are regulated by myosin light-chain phosphorylation. Myosin V transports cargo by walking along actin filaments.
Microtubules are structurally more complex than actin filaments, but they are also highly dynamic and play comparably diverse and important roles in the cell. Microtubules are polymers of the protein tubulin. The tubulin subunit is itself a heterodimer formed from two closely related globular proteins called α-tubulin and β-tubulin, each comprising 445–450 amino acids, which are tightly bound together by noncovalent bonds (Figure 16–42A). These two tubulin proteins are found only in this heterodimer, and each α or β monomer has a binding site for one molecule of GTP. The GTP that is bound to α-tubulin is physically trapped at the dimer interface and is never hydrolyzed or exchanged; it can therefore be considered to be an integral part of the tubulin heterodimer structure. The nucleotide on the β-tubulin, in contrast, may be in either the GTP or the GDP form and is exchangeable within the soluble (unpolymerized) tubulin dimer.
Tubulin is found in all eukaryotic cells, and it exists in multiple isoforms. Yeast and human tubulins are 75% identical in amino acid sequence. In mammals, there are at least six forms of α-tubulin and a similar number of β-tubulins, each encoded by a different gene. The different forms of tubulin are very similar, and they generally copolymerize into mixed microtubules in the test tube. However, they can have distinct locations in cells and tissues and perform subtly different functions. As a striking example, mutations in a particular human β-tubulin gene give rise to a paralytic eye-movement disorder due to loss of ocular nerve function. Numerous human neurological diseases have been linked to specific mutations in different tubulin genes.
Figure 16–41 Myosin V carries cargo along actin filaments. (A) The lever arm of myosin V is long, allowing it to take a bigger step along an actin filament than myosin II (see Figure 16–29). (B) Myosin V transports cargo and organelles along actin cables, in this example moving a mitochondrion into the growing bud of a yeast cell.
Microtubules Are Hollow Tubes Made of Protofilaments