Class-I phosphoinositide 3-kinases (PI3Ks) have pivotal roles in many cellular responses to external stimuli. PI3Ks are activated by binding to RasGTP, which leads to the accumulation of phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] in the plasma membrane; these PtdIns(3,4,5)P3 patches then act as docking sites for effector proteins. PI3Ks are also involved in F-actin-driven processes, such as chemotaxis, phagocytosis and macropinocytosis, but in these instances, not much is known with regard to their role and mode of regulation. Oliver Hoeller and colleagues now (p. 4296) address this question in the amoebae Dictyostelium by generating a complete deletion series of the five class-I PI3Ks that are encoded in its genome. Analysing the quintuple deletion mutant, they find that PI3K function is dispensable for motility, chemotaxis and phagocytosis of bacteria but required for macropinocytosis; in particular, the formation of fluid-filled vesicles from membrane ruffles is abolished in the absence of PI3K. The authors then show that PI3Ks affect two steps in macropinocytosis. PI3K1 and PI3K2 are involved in the formation of the PtdIns(3,4,5)P3 patches from which macropinosomes originate, whereas PI3K4 is required at a later stage of vesicle formation. Furthermore, they demonstrate that RasS and RasG participate in the formation of macropinosomes and interact with PI3K1, PI3K2 and PI3K4, suggesting that these Ras-like proteins in Dictyostelium regulate PI3Ks by recruiting them to their site of action during macropinocytosis.
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IN THIS ISSUE| 15 September 2013
Roles of PI3Ks in macropinocytosis
Online Issn: 1477-9137
Print Issn: 0021-9533
© 2013. Published by The Company of Biologists Ltd
J Cell Sci (2013) 126 (18): e1804.
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Roles of PI3Ks in macropinocytosis. J Cell Sci 15 September 2013; 126 (18): e1804. doi:
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