Phosphatidylinositol 3-kinases and their roles in phagosome maturation

Phagosome maturation is a highly organized and sequential process that results in the formation of a microbicidal phagolysosome. This results in crucial contributions to innate and adaptive immunity through pathogen clearance and antigen presentation. Thus, it is important to understand the regulatory networks that control the extent and nature of phagosome maturation. PI3Ks are lipid kinases that catalyze the phosphorylation of the 3' position of the inositol ring. This enzyme family is divided into three classes based on structure and substrate preferences. Previously, only the class III PI3K, hVps34, was thought to contribute to phagosome maturation. Recent evidence, however, suggests important contributions by class I PI3Ks in bringing about the diverse phagosome maturation phenotypes. Class I PI3Ks have also been implicated in the activation of Rab GTPases that function in maturation, such as Rab14. In addition, recent studies have illuminated the overlap between phagosome maturation and autophagy, which itself is regulated by multiple classes of PI3K. Taken together, a picture of phagosome maturation is emerging in which multiple classes of PI3Ks are involved in modulating maturation phenotypes. This review summarizes the known contributions of PI3Ks to phagosome maturation. Special emphasis is placed on the impact of PI3Ks on different maturation outcomes stemming from the engagement of diverse phagocytic receptors and on Rab and Ca(2+) signaling cascades.