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Vol. 18, Issue 5, 1609-1620, May 2007
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*Department of Cell Biology and
Graduate Program in Microbiology and Molecular Genetics, Emory University School of Medicine, Atlanta, GA 30322; and
Department of Poultry Science, School of Agriculture, University of Georgia, Athens, GA 30602
Submitted June 13, 2006;
Revised January 24, 2007;
Accepted February 12, 2007
Monitoring Editor: Carole Parent
Scar/WAVE proteins, members of the conserved Wiskott-Aldrich syndrome (WAS) family, promote actin polymerization by activating the Arp2/3 complex. A number of proteins, including a complex containing Nap1, PIR121, Abi1/2, and HSPC300, interact with Scar/WAVE, though the role of this complex in regulating Scar function remains unclear. Here we identify a short N-terminal region of Dictyostelium Scar that is necessary and sufficient for interaction with HSPC300 and Abi in vitro. Cells expressing Scar lacking this N-terminal region show abnormalities in F-actin distribution, cell morphology, movement, and cytokinesis. This is true even in the presence of wild-type Scar. The data suggest that the first 96 amino acids of Scar are necessary for participation in a large-molecular-weight protein complex, and that this Scar-containing complex is responsible for the proper localization and regulation of Scar. The presence of mis-regulated or unregulated Scar has significant deleterious effects on cells and may explain the need to keep Scar activity tightly controlled in vivo either by assembly in a complex or by rapid degradation.
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The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Present address: Hunter Laboratory, Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Room 3050, Cambridge, MA 02138.
Address correspondence to: Charles L. Saxe (karl{at}cellbio.emory.edu)