SUMMARY PARAGRAPH for LAS17
Las17p/Bee1p is an activator of the Arp2/3 protein complex that nucleates branched actin filaments. It is the only S. cerevisiae homolog of the human Wiskott-Aldrich syndrome protein (WASP) (7, 1) and is a member of the larger WASP/SCAR/WAVE protein family. Las17p was identified biochemically as an essential nucleation factor in the reconstitution of cortical actin patches in vitro, and independently as a verprolin (Vrp1p/End5p)-interacting protein (8, 2). Las17p localizes with the Arp2/3 complex to actin patches, and disruption of LAS17 leads to the loss of actin patches and a block in endocytosis (1, 2, 3).
Las17p physically interacts with the Arp2/3 complex. This interaction requires the carboxy-terminal WA (WH2 [WASp homology 2] and A[acidic]) domain of Las17p and is dependent upon two subunits of the Arp2/3 complex, Arc15p and Arc19p (4). The WA domain is sufficient for Arp2/3 complex binding and activation in vitro (4). The WA domain shares sequence similarity and genetic redundancy with an acidic domain in myosin I (Myo3p and Myo5p in S. cerevisiae), which also interacts with the Arp2/3 complex (9). These proteins appear to function redundantly in the activation of the Arp2/3 complex, as combined deletions of the WA domain of Las17p and the type I myosins abolish actin nucleation at cortical actin patches (7).
Genetic and biochemical studies have identified numerous proteins that physically interact with Las17p. The WH1 domain of Las17p binds strongly to verprolin (Vrp1p/End5p), the yeast homolog of human WIP (WASP-interacting protein), which is involved in Las17p localization (10, 11). The proline-rich region of Las17p binds to SH3 domain-containing proteins, including Sla1p (an actin patch protein with a role in endocytosis), Bbc1p/Mti1p, Bzz1p/Lsb7p, Myo3p, Myo5p, Lsb1p, Lsb2p, Ysc84p, Sho1p, and Rvs167p (12, 1, 3, 13, 7, 14). Although the significance of many of these interactions is not known, they may regulate the activity of Las17p, and thus, the activity of the Arp2/3 complex. Unlike other WASP family members, Las17p does not contain a conserved Cdc42p-binding domain and does not appear to be regulated by auto-inhibition (12).
Last updated: 2003-12-19