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© The Rockefeller University Press, 0021-9525/1998//1325 $5.00
The Journal of Cell Biology, Volume 142, Number 5, , 1998 1325-1335

SCAR, a WASP-related Protein, Isolated as a Suppressor of Receptor Defects in Late Dictyostelium Development

Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322-3030

G protein–coupled receptors trigger the reorganization of the actin cytoskeleton in many cell types, but the steps in this signal transduction cascade are poorly understood. During Dictyostelium development, extracellular cAMP functions as a chemoattractant and morphogenetic signal that is transduced via a family of G protein–coupled receptors, the cARs. In a strain where the cAR2 receptor gene is disrupted by homologous recombination, the developmental program arrests before tip formation. In a genetic screen for suppressors of this phenotype, a gene encoding a protein related to the Wiskott-Aldrich Syndrome protein was discovered. Loss of this protein, which we call SCAR (suppressor of cAR), restores tip formation and most later development to cAR2^– strains, and causes a multiple-tip phenotype in a cAR2⁺ strain as well as leading to the production of extremely small cells in suspension culture. SCAR^–cells have reduced levels of F-actin staining during vegetative growth, and abnormal cell morphology and actin distribution during chemotaxis. Uncharacterized homologues of SCAR have also been identified in humans, mouse, Caenorhabditis elegans, and Drosophila. These data suggest that SCAR may be a conserved negative regulator of G protein-coupled signaling, and that it plays an important role in regulating the actin cytoskeleton.

Key Words: Dictyostelium • WASP • actin cytoskeleton • G protein–coupled receptors • REMI

Abbreviations used in this paper: ABM-2, actin-based motility type 2 repeat; DB, developmental buffer; EST, expressed sequence tag; REMI, restriction enzyme–mediated integration; SCAR, suppressor of cAR; SH3, Src homology 3 domain; SHD, SCAR Homology domain; WASP, Wiskott-Aldrich syndrome protein; WH2, WASP homology 2 domain; WT, wild-type.

Address all correspondence to Charles L. Saxe III, Department of Cell Biology, Emory University School of Medicine, 1648 Pierce Drive, Atlanta, GA 30322. Tel.: 404-727-6248; Fax: 404-727-6256; E-mail: karl{at}cellbio.emory.edu

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