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Type I phosphatidylinositol 4-phosphate 5-kinase controls neutrophil polarity and directional movement

2007; Rockefeller University Press; Volume: 179; Issue: 7 Linguagem: Inglês

10.1083/jcb.200705044

1540-8140

Rosa Ana Lacalle, Rosa M. Peregil, Juan Pablo Albar, Ernesto Merino, Carlos Martínez‐A, Isabel Mérida, Santos Mañes,

Cell Adhesion Molecules Research

Directional cell movement in response to external chemical gradients requires establishment of front-rear asymmetry, which distinguishes an up-gradient protrusive leading edge, where Rac-induced F-actin polymerization takes place, and a down-gradient retractile tail (uropod in leukocytes), where RhoA-mediated actomyosin contraction occurs. The signals that govern this spatial and functional asymmetry are not entirely understood. We show that the human type I phosphatidylinositol 4-phosphate 5-kinase isoform beta (PIPKIbeta) has a role in organizing signaling at the cell rear. We found that PIPKIbeta polarized at the uropod of neutrophil-differentiated HL60 cells. PIPKIbeta localization was independent of its lipid kinase activity, but required the 83 C-terminal amino acids, which are not homologous to other PIPKI isoforms. The PIPKIbeta C terminus interacted with EBP50 (4.1-ezrin-radixin-moesin (ERM)-binding phosphoprotein 50), which enabled further interactions with ERM proteins and the Rho-GDP dissociation inhibitor (RhoGDI). Knockdown of PIPKIbeta with siRNA inhibited cell polarization and impaired cell directionality during dHL60 chemotaxis, suggesting a role for PIPKIbeta in these processes.