Abstract
Phosphoinositides are lipids involved in the vesicular transport of proteins and lipids between the different compartments of eukaryotic cells. They act by recruiting and/or activating effector proteins and thus are involved in regulating various cellular functions, such as vesicular budding, membrane fusion and cytoskeleton dynamics. Although detected in small concentrations in membranes, their role is essential to cell function, since imbalance in their concentrations is a hallmark of many cancers. Their synthesis involves phosphorylating/dephosphorylating positions D3, D4 and/or D5 of their inositol ring by specific lipid kinases and phosphatases. This process is tightly regulated and specific to the different intracellular membranes. Most enzymes involved in phosphoinositide synthesis are conserved between yeast and human, and their loss of function leads to severe diseases (cancer, myopathy, neuropathy and ciliopathy).
Highlights
Phosphoinositides are lipids involved in the vesicular transport of proteins and lipids between the different compartments of eukaryotic cells
The lipid bilayer of membranes has an asymmetric phospholipid composition between the inner and the outer leaflet, which partly results from the vertical diffusion between the two leaflets by a flip-flop mechanism with a low intrinsic rate compensated by the presence of proteins called flippases [3,4]
Upon autophagy induction, a protein complex comprising VPS34, VPS15, Beclin1 and ATG14 is formed at Endoplasmic Reticulum (ER) membranes, where the lipid kinase activity of VPS34 leads to the formation of PtdIns3P-enriched regions [58]
Summary
The dynamic modulation of the physicochemical properties of membranes is required for eukaryotic cells function. If the plasma membrane plays an essential role as a selective barrier, there are many more intracellular membrane structures in eukaryotic cells, such as organelles and transport vesicles. Both the organization, as well as the composition of these membranes depends on the nature of the compartment. The inositol ring of PPIn is a polyol cyclohexane of which positions D3, D4 and D5 can be phosphorylated, generating seven possible PPIn (Figure 1B): phosphatidylinositol 3-phosphate (PtdIns3P), PtdIns4P, PtdIns5P, PtdIns 3,4-bisphosphate (PtdIns(3,4)P2), PtdIns(3,5)P2, PtdIns(4,5)P2 and PtdIns 3,4,5-trisphosphate (PtdIns(3,4,5)P3) Despite their low concentration in membranes, PPIn play an essential role in the recruitment and/or activation of effector proteins. The name of the yeast enzyme (when relevant) is written on top of its human homologue
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