Departments of Medicine, University of British Columbia, Faculties of Medicine and Science, and Vancouver Coastal Health Research Institute (VCHRI), Vancouver, British Columbia, Canada.
J Leukoc Biol. 2012 Sep;92(3):553-66. doi: 10.1189/jlb.0212053. Epub 2012 May 8.
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.
吞噬体成熟是一个高度组织化和有序的过程，导致形成一个杀菌性的吞噬溶酶体。这通过病原体清除和抗原呈递对先天和适应性免疫做出了至关重要的贡献。因此，了解控制吞噬体成熟程度和性质的调节网络非常重要。PI3Ks 是脂质激酶，可催化肌醇环 3'位的磷酸化。该酶家族根据结构和底物偏好分为三类。以前，只有 III 类 PI3K（hVps34）被认为对吞噬体成熟有贡献。然而，最近的证据表明，I 类 PI3Ks 在带来不同的吞噬体成熟表型方面有重要贡献。I 类 PI3Ks 也参与了 Rab GTPases 的激活，这些 GTPases在成熟过程中起作用，如 Rab14。此外，最近的研究阐明了吞噬体成熟和自噬之间的重叠，自噬本身受多种 PI3K 类的调节。综上所述，吞噬体成熟的图景正在出现，其中多种 PI3K 类参与调节成熟表型。本文综述了 PI3Ks 对吞噬体成熟的已知贡献。特别强调了 PI3Ks 对不同成熟结果的影响，这些结果源自不同吞噬受体的参与以及 Rab 和 Ca2+信号级联。
