We recently showed that production of phosphatidylinositol 5-phosphate (PtdIns5P or PI5P) upon growth factor stimulation is important for cell migration. However, it was not entirely clear if PI5P itself could be a second messenger in cell migration, or, if it was rather an intermediate for the production of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2 or PI(4,5)P2). Indeed, PI5P can be converted to PI(4,5)P2 by type II PIP4 kinases (PIP4K2s). We therefore decided to knock down PIP4K2α by siRNA to test if further conversion of PI5P to PI(4,5)P2 is important for cell migration. Even though we obtained an efficient knockdown of PIP4K2α in BJ human fibroblasts, we did not observe any change in cell velocity. Conversely, ectopic overexpression of PIP4K2α would consume PI5P to produce PI(4,5)P2 and we found that overexpressing PIP4K2α decreased cell migration speed. Taken together, the data clearly indicate that it is PI5P, and not PI(4,5)P2 produced from PI5P, that is the crucial signaling molecule in cell migration. We conclude, therefore, that PI5P is a true second messenger important for cell migration.
Keywords: MTMR3; PI5P; PIKfyve; PIP4K2α; cell migration.