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Vol. 16, Issue 6, 2947-2959, June 2005

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The PCH Family Member MAYP/PSTPIP2 Directly Regulates F-Actin Bundling and Enhances Filopodia Formation and Motility in Macrophages

Violeta Chitu ^*, Fiona J. Pixley ^*, Frank Macaluso  , Daniel R. Larson , John Condeelis  , Yee-Guide Yeung ^*, and E. Richard Stanley ^*

^* Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461; Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461; and Analytical Imaging Facility, Albert Einstein College of Medicine, Bronx, NY 10461

Submitted October 21, 2004; Revised March 2, 2005; Accepted March 15, 2005
Monitoring Editor: David Drubin

Macrophage actin-associated tyrosine phosphorylated protein (MAYP) belongs to the Pombe Cdc15 homology (PCH) family of proteins involved in the regulation of actin-based functions including cell adhesion and motility. In mouse macrophages, MAYP is tyrosine phosphorylated after activation of the colony-stimulating factor-1 receptor (CSF-1R), which also induces actin reorganization, membrane ruffling, cell spreading, polarization, and migration. Because MAYP associates with F-actin, we investigated the function of MAYP in regulating actin organization in macrophages. Overexpression of MAYP decreased CSF-1–induced membrane ruffling and increased filopodia formation, motility and CSF-1-mediated chemotaxis. The opposite phenotype was observed with reduced expression of MAYP, indicating that MAYP is a negative regulator of CSF-1–induced membrane ruffling and positively regulates formation of filopodia and directional migration. Overexpression of MAYP led to a reduction in total macrophage F-actin content but was associated with increased actin bundling. Consistent with this, purified MAYP bundled F-actin and regulated its turnover in vitro. In addition, MAYP colocalized with cortical and filopodial F-actin in vivo. Because filopodia are postulated to increase directional motility by acting as environmental sensors, the MAYP-stimulated increase in directional movement may be at least partly explained by enhancement of filopodia formation.

Abbreviations used: AFU, arbitrary fluorescence units; CIP4, Cdc42-associated protein 4; CSF-1, colony-stimulating factor-1; CSF-1R, colony-stimulating factor-1 receptor; FCH, Fes-CIP4 homology domain; GFP, green fluorescent protein; IRES, internal ribosomal entry site; MAYP, macrophage actin-associated tyrosine-phosphorylated protein; MSCV, murine stem cell virus; NMAYP-C, rabbit IgG anti-MAYP preabsorbed with nuclear extract; N-WASP, neural WASP; PEST, proline-glutamic acid-serine-threonine–rich; PSTPIP, proline serine threonine phosphatase–interacting protein; PCH, Pombe Cdc15 homology; RaIgG, preimmune rabbit immunoglobulin G; RPE, relative plating efficiency; SEM, scanning electron microscopy; SH3, Src homology domain 3; Syndapin, synaptic dynamin-associated protein; WASP, Wiskott-Aldrich syndrome protein.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: E. Richard Stanley (rstanley{at}aecom.yu.edu).

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