Arp2/3 complex-independent actin regulatory function of WAVE.
We report that WAVE1/Scar1, a WASP-family protein that functions downstream of Rac in membrane ruffling, can induce part of the reorganization of the actin cytoskeleton without Arp2/3 complex. WAVE1 has been reported to associate and activate Arp2/3 complex at its C-terminal region that is rich in acidic residues. The deletion of the acidic residues abolished the interaction with and the activation ability of Arp2/3 complex. The expression of the mutant WAVE1 lacking the acidic residues (DeltaA), however, induced actin-clustering in cells as the wild-type WAVE1 did. In addition, this actin-clustering could not be suppressed by the coexpression of the Arp2/3 complex-sequestering fragment (CA-region) derived from N-WASP, which clearly inhibits Rac-induced membrane ruffling. This study therefore demonstrates that WAVE1 reorganizes the actin cytoskeleton not only through Arp2/3 complex but also through another unidentified mechanism that may be important but has been neglected thus far.
Sasaki
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Department of Biochemistry, Institute of Medical Science, University of Tokyo, Japan.
Miki
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H
Takenawa
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T
D016475:3T3 Cells; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001704:Biopolymers / Q000378:metabolism; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D051300:Wiskott-Aldrich Syndrome Protein Family; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; C495927:Actr2 protein, mouse; C495929:Actr3 protein, mouse; D001704:Biopolymers; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C495774:Wasf1 protein, mouse; C495772:Wasl protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal