| | |  | | | | Record from Web of Science® | | | | | | |
| Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex |
|
|
| Author(s): Machesky LM, Insall RH |
| Source: CURRENT BIOLOGY Volume: 8 Issue: 25 Pages: 1347-1356 Published: DEC 17 1998 |
| Times Cited: 461 References: 39 |
| Abstract: Background: The actin-related proteins Arp2 and Arp3 are part of a seven-protein complex which is localized in the lamellipodia of a variety of cell types, and in actin-rich spots of unknown function. The Arp2/3 complex enhances actin nucleation and causes branching and crosslinking of actin filaments in vitro; in vivo it is thought to drive the formation of lamellipodia and to be a control center for actin-based motility. The Wiskott-Aldrich syndrome protein, WASP, is an adaptor protein implicated in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Scar1 is a member of a new family of proteins related to WASP, and it may also have a role in regulating the actin cytoskeleton. Scar1 is the human homologue of Dictyostelium Scar1, which is thought to connect G-protein-coupled receptors to the actin cytoskeleton. The mammalian Scar family contains at least four members. We have examined the relationships between WASP, Scar1, and the Arp2/3 complex. Results: We have identified WASP and its relative Scar1 as proteins that interact with the Arp2/3 complex. We have used deletion analysis to show that both WASP and Scar1 interact with the p21 subunit of the Arp2/3 complex through their carboxyl termini. Overexpression of carboxy-terminal fragments of Scar1 or WASP in cells caused a disruption in the localization of the Arp2/3 complex and, concomitantly, induced a complete loss of lamellipodia and actin spots. The induction of lamellipodia by platelet-derived growth factor was also suppressed by overexpression of the fragment of Scar1 that binds to the Arp2/3 complex.
Conclusions: We have identified a conserved sequence domain in proteins of the WASP family that binds to the Arp2/3 complex. Overexpression of this domain in cells disrupts the localization of the Arp2/3 complex and inhibits lamellipodia formation. Our data suggest that WASP-related proteins may regulate the actin cytoskeleton through the Arp2/3 complex.
|
| Document Type: Article |
| Language: English |
| Reprint Address: Machesky, LM (reprint author), Univ Birmingham, Sch Biochem, POB 363, Birmingham B15 2TT, W Midlands England |
Addresses:
1. UCL, Dept Mol Med, MRC, LMCB, London WC1E 6BT, England
2. UCL, Dept Physiol, MRC, LMCB, London WC1E 6BT, England |
| Publisher: CURRENT BIOLOGY LTD, 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 151VC |
| ISSN: 0960-9822 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |