Abstract
Despite their comparatively low abundance in biological membranes, phosphoinositides are key to the regulation of a diverse array of signaling pathways and direct membrane traffic. The role of phosphoinositides in the initiation and progression of endocytic pathways has been studied in considerable depth. Recent advances have revealed that distinct phosphoinositide species feature prominently in clathrin-dependent and -independent endocytosis as well as in phagocytosis and macropinocytosis. Moreover, a variety of intracellular and cell-associated pathogens have developed strategies to commandeer host cell phosphoinositide metabolism to gain entry and/or metabolic advantage, thereby promoting their survival and proliferation. Here, we briefly survey the current knowledge on the involvement of phosphoinositides in endocytosis, phagocytosis, and macropinocytosis and highlight several examples of molecular mimicry employed by pathogens to either “hitch a ride” on endocytic pathways endogenous to the host or create an entry path of their own.
Highlights
Despite their comparatively low abundance in biological membranes, phosphoinositides are key to the regulation of a diverse array of signaling pathways and direct membrane traffic
Introduction: phosphoinositides and the internalization of the extracellular milieu The seven phosphoinositides, which form through combinatory phosphorylation of the inositol ring at positions D3, D4, and D5 (Figure 1A), are present primarily on the cytosolic surface of biological membranes
Phosphoinositides are dynamic; their abundance and subcellular distribution are regulated in both time and space by active phosphorylation and dephosphorylation reactions as well as by transport between organelles via both vesicular and non-vesicular traffic
Summary
F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. Despite acting as a phosphatase, SopB mediates the formation of the 3-phosphorylated species PtdIns(3,4,5)P3 and PtdIns(3,4)P2 at invasion ruffles[200,201] (Figure 2A) These phosphoinositides recruit and activate AKT through its PH domain, thereby promoting host cell survival following infection[202,203]. Rather than favoring sustained accumulation of PtdIns(3,4,5)P3, the phosphatase activity of SHIP2 generates a local platform rich in PtdIns(3,4)P2 in the pedestal (Figure 2C) The latter inositide is sensed by the PH domain of lamellipodin, which is recruited to modulate F-actin polymerization in the pedestal[67,237]. Whether and how these lipids participate in membrane internalization and pathogen invasion remains to be studied as we await the development of suitable analytical tools
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