PI3Ks and small GTPases in neutrophil migration: Two sides of the same coin

Cell migration is a key event in physiological processes such as embryonic development, tissue repair, angiogenesis and immune responses. Alteration of the migration program is an important component in multiple pathologies, including chronic inflammation, autoimmunity and tumor metastasis. Understanding of the precise mechanisms at the basis of cellular migration may lead to the identification of novel therapeutic approach for these diseases. Recent evidences show that the interplay between the lipid kinases phosphatidylinositol 3-kinase (PI3Ks) and small GTPases play a critical role in driving cell migration. In this review we will describe the role of these molecules and the interaction between their signal cascades in leukocyte polarization and amoeboid migration.

► PI3Ks produce PIP3 at the leading edge inducing cell polarity.
► Principal PIP3 effectors are regulators of small GTPases.
► Different family of small GTPases, like Arf and Rho, are mutually regulated.