Normal Arp2/3 complex activation in platelets lacking WASp. Blood 2002 Sep 15;100(6):2113-22
Date
08/30/2002Pubmed ID
12200375Scopus ID
2-s2.0-0037105573 (requires institutional sign-in at Scopus site) 61 CitationsAbstract
Arp2/3 complex is believed to induce de novo nucleation of actin filaments at the edge of motile cells downstream of WASp family proteins. In this study, the signaling pathways leading to Arp2/3 complex activation, actin assembly, and shape change were investigated in platelets isolated from patients with Wiskott-Aldrich Syndrome (WAS), that is, who lack WASp, and in WASp-deficient mouse platelets. WASp-deficient human and mouse platelets elaborate filopodia, spread lamellae, and assemble actin, identical to control WASp-expressing platelets. Human platelets contain 2 microM Arp2/3 complex, or 8600 molecules/cell. Arp2/3 complex redistributes to the edge of the lamellae and to the Triton X-100-insoluble actin cytoskeleton of activated WASp-deficient platelets. Furthermore, the C-terminal CA domain of N-WASp, which sequesters Arp2/3 complex, inhibits by half the actin nucleation capacity of octylglucoside-permeabilized and activated WAS platelets, similar to its effect in WASp-expressing cells. Along with WASp, platelets express WAVE-2 as a physiologic activator of Arp2/3 complex and a small amount of N-WASp. Taken together, our findings show that platelets activate Arp2/3 complex, assemble actin, and change shape in the absence of WASp, indicating a more specialized role for WASp in these cells.
Author List
Falet H, Hoffmeister KM, Neujahr R, Hartwig JHAuthors
Herve Falet PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinKarin Hoffmeister MD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Actin-Related Protein 2Actin-Related Protein 3
Actins
Animals
Blood Platelets
Cell Size
Cytoskeletal Proteins
Humans
Mice
Platelet Adhesiveness
Protein Binding
Proteins
Signal Transduction
Wiskott-Aldrich Syndrome
Wiskott-Aldrich Syndrome Protein
