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In response to upstream signals, proteins in the Wiskott-Aldrich Syndrome protein (WASP) family regulate actin nucleation via the Arp2/3 complex. Despite intensive study of the function of WASP family proteins in nucleation, it is not yet understood how their distinct structural organization contributes to actin-based motility. Herein, we analyzed the activities of WASP and Scar1 truncation derivatives by using a bead-based motility assay. The minimal region of WASP sufficient to direct movement was the C-terminal WCA fragment, whereas the corresponding region of Scar1 was insufficient. In addition, the proline-rich regions of WASP and Scar1 and the Ena/VASP homology 1 (EVH1) domain of WASP independently enhanced motility rates. The contributions of these regions to motility could not be accounted for by their direct effects on actin nucleation with the Arp2/3 complex, suggesting that they stimulate motility by recruiting additional factors. We have identified profilin as one such factor. WASP- and Scar1-coated bead motility rates were significantly reduced by depletion of profilin and VASP and could be more efficiently rescued by a combination of VASP and wild-type profilin than by VASP and a mutant profilin that cannot bind proline-rich sequences. Moreover, motility of WASP WCA beads was not affected by the depletion or addback of VASP and profilin. Our results suggest that recruitment of factors, including profilin, by the proline-rich regions of WASP and Scar1 and the EVH1 domain of WASP stimulates cellular actin-based motility.
Antón,
The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck.
1998, Pubmed
Antón,
The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck.
1998,
Pubmed
Bachmann,
The EVH2 domain of the vasodilator-stimulated phosphoprotein mediates tetramerization, F-actin binding, and actin bundle formation.
1999,
Pubmed
Bear,
Regulating cellular actin assembly.
2001,
Pubmed
Bear,
Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility.
2002,
Pubmed
Bernheim-Groswasser,
The dynamics of actin-based motility depend on surface parameters.
2002,
Pubmed
Björkegren-Sjögren,
Isolation and characterization of two mutants of human profilin I that do not bind poly(L-proline).
1997,
Pubmed
Blanchoin,
Direct observation of dendritic actin filament networks nucleated by Arp2/3 complex and WASP/Scar proteins.
2000,
Pubmed
Cameron,
Motility of ActA protein-coated microspheres driven by actin polymerization.
1999,
Pubmed
Carlier,
GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex.
2000,
Pubmed
Castellano,
A WASp-VASP complex regulates actin polymerization at the plasma membrane.
2001,
Pubmed
Cooper,
Pyrene actin: documentation of the validity of a sensitive assay for actin polymerization.
1983,
Pubmed
Egile,
Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility.
1999,
Pubmed
Fukuoka,
A novel neural Wiskott-Aldrich syndrome protein (N-WASP) binding protein, WISH, induces Arp2/3 complex activation independent of Cdc42.
2001,
Pubmed
Geese,
Contribution of Ena/VASP proteins to intracellular motility of listeria requires phosphorylation and proline-rich core but not F-actin binding or multimerization.
2002,
Pubmed
Higgs,
Influence of the C terminus of Wiskott-Aldrich syndrome protein (WASp) and the Arp2/3 complex on actin polymerization.
1999,
Pubmed
Higgs,
Activation by Cdc42 and PIP(2) of Wiskott-Aldrich syndrome protein (WASp) stimulates actin nucleation by Arp2/3 complex.
2000,
Pubmed
Janmey,
Polyproline affinity method for purification of platelet profilin and modification with pyrene-maleimide.
1991,
Pubmed
Kellogg,
Behaviour of microtubules and actin filaments in living Drosophila embryos.
1988,
Pubmed
Kim,
Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein.
2000,
Pubmed
Korenbaum,
The role of profilin in actin polymerization and nucleotide exchange.
1998,
Pubmed
Kouyama,
Fluorimetry study of N-(1-pyrenyl)iodoacetamide-labelled F-actin. Local structural change of actin protomer both on polymerization and on binding of heavy meromyosin.
1981,
Pubmed
Lasa,
The amino-terminal part of ActA is critical for the actin-based motility of Listeria monocytogenes; the central proline-rich region acts as a stimulator.
1995,
Pubmed
,
Xenbase
Laurent,
Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes.
1999,
Pubmed
Loisel,
Reconstitution of actin-based motility of Listeria and Shigella using pure proteins.
1999,
Pubmed
Ma,
Corequirement of specific phosphoinositides and small GTP-binding protein Cdc42 in inducing actin assembly in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Machesky,
Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex.
,
Pubmed
Machesky,
Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex.
1999,
Pubmed
Marchand,
Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex.
2001,
Pubmed
Marchand,
Actin-based movement of Listeria monocytogenes: actin assembly results from the local maintenance of uncapped filament barbed ends at the bacterium surface.
1995,
Pubmed
,
Xenbase
Martinez-Quiles,
WIP regulates N-WASP-mediated actin polymerization and filopodium formation.
2001,
Pubmed
May,
The Arp2/3 complex is essential for the actin-based motility of Listeria monocytogenes.
1999,
Pubmed
Miki,
IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling.
2000,
Pubmed
Miki,
N-WASP, a novel actin-depolymerizing protein, regulates the cortical cytoskeletal rearrangement in a PIP2-dependent manner downstream of tyrosine kinases.
1996,
Pubmed
Miki,
Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP.
1998,
Pubmed
Miki,
WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac.
1998,
Pubmed
Mimuro,
Profilin is required for sustaining efficient intra- and intercellular spreading of Shigella flexneri.
2000,
Pubmed
,
Xenbase
Pantaloni,
How profilin promotes actin filament assembly in the presence of thymosin beta 4.
1993,
Pubmed
Prehoda,
Integration of multiple signals through cooperative regulation of the N-WASP-Arp2/3 complex.
2000,
Pubmed
Ramesh,
WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells.
1997,
Pubmed
Reinhard,
The proline-rich focal adhesion and microfilament protein VASP is a ligand for profilins.
1995,
Pubmed
Rohatgi,
Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4, 5-bisphosphate.
2000,
Pubmed
,
Xenbase
Rohatgi,
The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly.
1999,
Pubmed
,
Xenbase
Rohatgi,
Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway.
2001,
Pubmed
Schindelhauer,
Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product.
1996,
Pubmed
Skoble,
Pivotal role of VASP in Arp2/3 complex-mediated actin nucleation, actin branch-formation, and Listeria monocytogenes motility.
2001,
Pubmed
Skoble,
Three regions within ActA promote Arp2/3 complex-mediated actin nucleation and Listeria monocytogenes motility.
2000,
Pubmed
Spudich,
The regulation of rabbit skeletal muscle contraction. I. Biochemical studies of the interaction of the tropomyosin-troponin complex with actin and the proteolytic fragments of myosin.
1971,
Pubmed
Suetsugu,
Requirement of the basic region of N-WASP/WAVE2 for actin-based motility.
2001,
Pubmed
Suetsugu,
The essential role of profilin in the assembly of actin for microspike formation.
1998,
Pubmed
Suetsugu,
Identification of another actin-related protein (Arp) 2/3 complex binding site in neural Wiskott-Aldrich syndrome protein (N-WASP) that complements actin polymerization induced by the Arp2/3 complex activating (VCA) domain of N-WASP.
2001,
Pubmed
Sun,
Actin monomer binding proteins.
1995,
Pubmed
Suzuki,
Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri.
1998,
Pubmed
,
Xenbase
Symons,
Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.
1996,
Pubmed
Takenawa,
WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement.
2001,
Pubmed
Theriot,
The rate of actin-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization.
1992,
Pubmed
Theriot,
Involvement of profilin in the actin-based motility of L. monocytogenes in cells and in cell-free extracts.
1994,
Pubmed
,
Xenbase
Welch,
Purification and assay of the platelet Arp2/3 complex.
1998,
Pubmed
Winter,
Activation of the yeast Arp2/3 complex by Bee1p, a WASP-family protein.
1999,
Pubmed
Yamaguchi,
Two tandem verprolin homology domains are necessary for a strong activation of Arp2/3 complex-induced actin polymerization and induction of microspike formation by N-WASP.
2000,
Pubmed
Yang,
Profilin enhances Cdc42-induced nucleation of actin polymerization.
2000,
Pubmed
Yarar,
The Wiskott-Aldrich syndrome protein directs actin-based motility by stimulating actin nucleation with the Arp2/3 complex.
1999,
Pubmed
Zalevsky,
Different WASP family proteins stimulate different Arp2/3 complex-dependent actin-nucleating activities.
2001,
Pubmed
