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.