Vaccine Lab / Alfa Chemistry
Phosphoinositide Series
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Phosphoinositide Series

Phosphoinositides are a family of phospholipids containing inositol that are present in all eukaryotic cells. The founding member of this family is the unphosphorylated phosphatidylinositol (PtdIns), primarily synthesized in the endoplasmic reticulum and then delivered to other membranes by vesicular transport or via cytosolic PtdIns transfer protein [1]. Phosphoinositides then derives from the phosphorylation of hydroxyl groups in the myo-inositol head group of PtdIns. It is well known that phosphoinositide has a low abundance in total cellular lipids. But they still receive a lot of attention from researchers. This is mainly due to the fact that such phospholipids not only have structural functions, but also play a key role in important cellular processes.

Structure of phosphoinositide

Like phospholipids, phosphoinositide has a glycerol backbone, esterified to two fatty acid chains and a phosphate, and attached to a polar head group that extends into the cytoplasm. For phosphoinositides, the head group is the cyclic polyol myo-inositol. This inositol head group has free hydroxyl groups at positions D2 through D6, and those at positions D3, D4 and D5 are readily phosphorylated by cytoplasmic lipid kinases [2]. The structure of phosphoinositide is complex. Phosphorylation at different positions in the head group may combine to produce seven distinct, but interconvertible, derivatives: phosphatidylinositol 3-phosphate (PtdIns-3-P), PtdIns-4-P, PtdIns-5-P, phosphatidylinositol 3,5-bisphosphate (PtdIns-3,5-P2), PtdIns-4,5-P2, PtdIns-3,4-P2, and phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3).

Generic structure of phosphoinositides, showing three phosphorylatable positions, D3, D4, and D5, on the myo-inositol headgroup.Figure 1. Generic structure of phosphoinositides, showing three phosphorylatable positions, D3, D4, and D5, on the myo-inositol headgroup.

Biological functions of phosphoinositide

Phosphoinositides are not only a component of the cellular membrane, but also have different biological functions. First, the lipid tail of phosphoinositides forces them to bind to membranes. Thus, they can label specific membrane compartments or subdomains within membranes. Second, the soluble head groups of phosphoinositides allow them to bind to cytosolic proteins and to mediate the association of these proteins to specific membranes (spatial regulation). Finally, because some phosphoinositides are only synthesized upon cellular stimulation in normal cells, they can also temporally regulate the activation of target proteins.

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  1. Gilbert, D. P.; et al. Phosphoinositides in cell regulation and membrane dynamics. Nature. 2006, 443: 651-657.
  2. Hille, B.; et al. Phosphoinositides: lipid regulators of membrane proteins. J Physiol. 2010, 588: 3179-3185.

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