WIP, a protein associated with Wiskott–Aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells

WIP, a protein associated with Wiskott–Aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells

^*Division of Immunology, Children’s Hospital and ^¶Division of Experimental Medicine, Brigham and Women’s Hospital, and Departments of ^†Pediatrics and ^‖Medicine, Harvard Medical School, Boston, MA 02115

Communicated by Robert A. Good, University of South Florida, St. Petersburg, FL (received for review September 2, 1997)

Abstract

Wiskott–Aldrich syndrome (WAS) is an X-linked immunodeficiency caused by mutations that affect the WAS protein (WASP) and characterized by cytoskeletal abnormalities in hematopoietic cells. By using the yeast two-hybrid system we have identified a proline-rich WASP-interacting protein (WIP), which coimmunoprecipitated with WASP from lymphocytes. WIP binds to WASP at a site distinct from the Cdc42 binding site and has actin as well as profilin binding motifs. Expression of WIP in human B cells, but not of a WIP truncation mutant that lacks the actin binding motif, increased polymerized actin content and induced the appearance of actin-containing cerebriform projections on the cell surface. These results suggest that WIP plays a role in cortical actin assembly that may be important for lymphocyte function.

Footnotes

↵ ‡ N.R. and I.M.A. contributed equally to this work.
↵ § To whom reprint requests should be addressed.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF031588).
ABBREVIATIONS:

WAS,

Wiskott–Aldrich syndrome;

WASP,

WAS protein;

WIP,

WASP-interacting protein;

WH,

WASP homology;

GBD,

GTPase binding domain;

SH3,

Src homology 3;

GST,

glutathione S-transferase;

MBP,

maltose binding protein;

FITC,

fluorescein isothiocyanate