The Tails of Two Myosins

Two papers in this issue of The Journal of Cell Biology uncover a possible new connection between the actin-nucle-ating complex of proteins, the Arp2/3 complex, and the type I myosin motors. In this issue, Lechler et al. (2000) and Evangelista et al. (2000) show a direct interaction of the S. cerevisiae myosin I motors (Myo3p and Myo5p) with the Arp2/3 complex through an acidic COOH-terminal sequence motif. The data suggest that a large complex containing both myosin motors and actin nucleating proteins may be a functional unit for signal-induced actin assembly. Furthermore, both studies provide evidence that myosin I function is essential for assembly and maintenance of fila-mentous actin structures in cells. This is exciting and raises some controversy, given the recent discovery that intracel-lular pathogens such as Shigella flexnerii and Listeria monocytogenes do not use myosin motors to achieve actin-based motility (Loisel et al., 1999). Clearly, future research will be devoted to resolving the role of myosin I motor activity in actin-based motility in eukaryotic cells, as this may constitute a mechanistic difference between the Listeria and Shigella model systems and eukaryotic cell motility. The Arp2/3 complex nucleates new actin filament assembly , most likely in response to signals such as the activation of receptor tyrosine kinases or receptors coupled to small GTPases of the Rho family (e. It is named Arp2/3 because in addition to five unique polypeptides, it contains the actin-related proteins, Arp2 and Arp3. In vitro, the Arp2/3 complex cross-links actin filaments, caps the slow-growing (pointed) end of filaments (Mullins et al., 1998), and nucleates actin assembly (Mullins et al., 1998; Welch et al., 1998). This activity can be greatly stimulated by direct interaction with proteins of the WASP family (Machesky and Insall, 1999; Svitkina and Borisy, 1999). WASP family proteins are named for Wiskott-Aldrich syndrome, a fatal immune disease in humans that results from mutations in the gene encoding WASP (Thrasher et al., 1998). In S. cerevisiae , the single WASP family protein is called Las17p or Bee1p (Fig. 1). While the details of how the WASP family proteins activate the Arp2/3 complex are not yet known, a conserved acidic tail sequence in all WASP family members binds directly to the complex (Machesky et al., 1998; Winter et al., 1999). This sequence motif is highly homologous to the Myo3p and Myo5p acidic tail sequences (Fig. 1), suggesting that these myosins may connect to the Arp2/3 …