Phosphatidylinositol 4-kinase III beta regulates cell shape, migration and focal adhesion number.

Abstract

Cell shape is regulated by cell adhesion and cytoskeletal and membrane dynamics. Cell shape, adhesion and motility have a complex relationship and understanding them is important in understanding developmental patterning and embryogenesis. Here we show that the lipid kinase phosphatidylinositol 4-kinase III beta (PI4KIII{beta}) regulates cell shape, migration and Focal Adhesion (FA) number. PI4KIII{beta} generates phosphatidylinositol 4-phosphate from phosphatidylinositol and is highly expressed in a subset of human breast cancers. PI4KIII{beta} and the PI4P it generates regulate a variety of cellular functions, ranging from control of Golgi structure, fly fertility and Akt signaling. Here, we show that loss of PI4KIII{beta} expression decreases cell migration and alters cell shape in NIH3T3 fibroblasts. The changes are accompanied by an increase in the number of FA in cells lacking PI4KIII{beta}. Furthermore, we find that PI4P-containing vesicles move to the migratory leading-edge during migration and that some of these vesicles tether to and fuse with FA. Fusion is associated with FA disassembly. This suggests a novel regulatory role for PI4KIII{beta} and PI4P in cell adhesion and cell shape maintenance.