The PCH family member MAYP/PSTPIP2 directly regulates F-actin bundling and enhances filopodia formation and motility in macrophages.
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.
Chitu
Violeta
V
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Pixley
Fiona J
FJ
Macaluso
Frank
F
Larson
Daniel R
DR
Condeelis
John
J
Yeung
Yee-Guide
YG
Stanley
E Richard
ER
D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D048868:Adaptor Proteins, Signal Transducing / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D018715:Microscopy, Video; D010590:Phalloidine / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D012235:Rhodamines; D013347:Subcellular Fractions / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D005456:Fluorescent Dyes; C486383:Pstpip2 protein, mouse; D012235:Rhodamines; D010590:Phalloidine; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor