PLC-β2 activity on actin-associated polyphosphoinositides promotes migration of differentiating tumoral myeloid precursors

During both maturation and function, neutrophils are subjected to reorganization of the actin cytoskeleton. Among the molecules that influence cytoskeletal architecture, the amount and subcellular localization of phosphomositides, regulated by specific kinases and phosphatases, may play a crucial role. In neutrophils, PLC-beta 2 is a major phosphomositide-dependent phospholipase C isoform activated in response to chemoattractants, even though its role in the modifications of cell morphology and motility that occur during the inflammatory process has not been fully elucidated. In APL-derived promyelocytes induced to complete their maturation program, we have found that the expression levels of PLC-beta 2 positively correlate with the degree of the reached neutrophil differentiation. Here, we demonstrate that PLC-beta 2 modulates the migration capability of promyelocytes induced to differentiate with ATRA. In differentiating cells, the association of PLC-beta 2 with actin, mediated by the PH domain, seems crucial for catalytic activity. We conclude that phosphodiesterase activity of PLC-beta 2 on the actin-associated PIP2 may be responsible, by modifying the phosphomositide pools, for the modifications of cytoskeleton architecture that take place during motility of differentiating promyelocytes. (c) 2007 Elsevier Inc. All rights reserved.