QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 5, 2191-2206, May 2005

This Article Full Text Full Text (PDF) All Versions of this Article: E04-09-0844v1 16/5/2191    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Myers, S. A. Articles by Chung, C. Y. Search for Related Content PubMed PubMed Citation Articles by Myers, S. A. Articles by Chung, C. Y.

A Dictyostelium Homologue of WASP Is Required for Polarized F-Actin Assembly during Chemotaxis

Scott A. Myers ^*, Ji W. Han ^*, Yoonsung Lee ^* , Richard A. Firtel , and Chang Y. Chung ^* 

^* Department of Pharmacology, Vanderbilt University Medical Center, Nashville TN 37232-6600; Section of Cell and Developmental Biology, Division of Biological Sciences, Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093-0634

Submitted September 27, 2004; Revised February 11, 2005; Accepted February 15, 2005
Monitoring Editor: Martin A. Schwartz

The actin cytoskeleton controls the overall structure of cells and is highly polarized in chemotaxing cells, with F-actin assembled predominantly in the anterior leading edge and to a lesser degree in the cell's posterior. Wiskott-Aldrich syndrome protein (WASP) has emerged as a central player in controlling actin polymerization. We have investigated WASP function and its regulation in chemotaxing Dictyostelium cells and demonstrated the specific and essential role of WASP in organizing polarized F-actin assembly in chemotaxing cells. Cells expressing very low levels of WASP show reduced F-actin levels and significant defects in polarized F-actin assembly, resulting in an inability to establish axial polarity during chemotaxis. GFP-WASP preferentially localizes at the leading edge and uropod of chemotaxing cells and the B domain of WASP is required for the localization of WASP. We demonstrated that the B domain binds to PI(4,5)P₂ and PI(3,4,5)P₃ with similar affinities. The interaction between the B domain and PI(3,4,5)P₃ plays an important role for the localization of WASP to the leading edge in chemotaxing cells. Our results suggest that the spatial and temporal control of WASP localization and activation is essential for the regulation of directional motility.

Present address: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710.

Address correspondence to: Chang Y. Chung (chang.chung{at}vanderbilt.edu).

This article has been cited by other articles:

				K. M. Cooper, D. A. Bennin, and A. Huttenlocher The PCH Family Member Proline-Serine-Threonine Phosphatase-interacting Protein 1 Targets to the Leukocyte Uropod and Regulates Directed Cell Migration Mol. Biol. Cell, August 1, 2008; 19(8): 3180 - 3191. [Abstract] [Full Text] [PDF]

				D. Caracino, C. Jones, M. Compton, and C. L. Saxe III The N-Terminus of Dictyostelium Scar Interacts with Abi and HSPC300 and Is Essential for Proper Regulation and Function Mol. Biol. Cell, May 1, 2007; 18(5): 1609 - 1620. [Abstract] [Full Text] [PDF]

				K. Szczur, H. Xu, S. Atkinson, Y. Zheng, and M.-D. Filippi Rho GTPase CDC42 regulates directionality and random movement via distinct MAPK pathways in neutrophils Blood, December 15, 2006; 108(13): 4205 - 4213. [Abstract] [Full Text] [PDF]

				J. W. Han, L. Leeper, F. Rivero, and C. Y. Chung Role of RacC for the Regulation of WASP and Phosphatidylinositol 3-Kinase during Chemotaxis of Dictyostelium J. Biol. Chem., November 17, 2006; 281(46): 35224 - 35234. [Abstract] [Full Text] [PDF]

				B. P. Somesh, G. Vlahou, M. Iijima, R. H. Insall, P. Devreotes, and F. Rivero RacG Regulates Morphology, Phagocytosis, and Chemotaxis Eukaryot. Cell, October 1, 2006; 5(10): 1648 - 1663. [Abstract] [Full Text] [PDF]

				S. A. Myers, L. R. Leeper, and C. Y. Chung WASP-interacting Protein Is Important for Actin Filament Elongation and Prompt Pseudopod Formation in Response to a Dynamic Chemoattractant Gradient Mol. Biol. Cell, October 1, 2006; 17(10): 4564 - 4575. [Abstract] [Full Text] [PDF]

				D. M. Veltman and P. J.M. Van Haastert Guanylyl Cyclase Protein and cGMP Product Independently Control Front and Back of Chemotaxing Dictyostelium Cells Mol. Biol. Cell, September 1, 2006; 17(9): 3921 - 3929. [Abstract] [Full Text] [PDF]