PLC-beta2 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 phosphoinositides, regulated by specific kinases and phosphatases, may play a crucial role. In neutrophils, PLC-beta2 is a major phosphoinositide-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-beta2 positively correlate with the degree of the reached neutrophil differentiation. Here, we demonstrate that PLC-beta2 modulates the migration capability of promyelocytes induced to differentiate with ATRA. In differentiating cells, the association of PLC-beta2 with actin, mediated by the PH domain, seems crucial for catalytic activity. We conclude that phosphodiesterase activity of PLC-beta2 on the actin-associated PIP2 may be responsible, by modifying the phosphoinositide pools, for the modifications of cytoskeleton architecture that take place during motility of differentiating promyelocytes.
Brugnoli
Federica
F
Signal Transduction Unit, Laboratory of Cell Biology, Section of Human Anatomy, Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy.
Bavelloni
Alberto
A
Benedusi
Mascia
M
Capitani
Silvano
S
Bertagnolo
Valeria
V
D000199:Actins / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D042381:Granulocyte Precursor Cells / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D054799:Phospholipase C beta; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D007527:Isoenzymes; D018129:Phosphatidylinositol Phosphates; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D010738:Type C Phospholipases; C518036:PLCB2 protein, human; D054799:Phospholipase C beta