Abstract
Polyphosphoinositides (PPIns) are a family of seven lipid messengers that regulate a vast array of signalling pathways to control cell proliferation, migration, survival and differentiation. PPIns are differentially present in various sub-cellular compartments and, through the recruitment and regulation of specific proteins, are key regulators of compartment identity and function. Phosphoinositides and the enzymes that synthesise and degrade them are also present in the nuclear membrane and in nuclear membraneless compartments such as nuclear speckles. Here we discuss how PPIns in the nucleus are modulated in response to external cues and how they function to control downstream signalling. Finally we suggest a role for nuclear PPIns in liquid phase separations that are involved in the formation of membraneless compartments within the nucleus.
Highlights
Polyphosphoinositides (PPIns) are a family of phospholipids that are derived from phosphorylation of the parent molecule Phosphatidylinositol (PtdIns)
The regulation and function of nuclear phosphoinositides is likely to be important to determine how mutations in PPIns modulators impact on disease manifestation
While analysis of these mutations might initially appear to be explained by their cytoplasmic functions, the phenotypes observed in human disease, such as Lowe syndrome, are often complex and difficult to rationalise [133]
Summary
Polyphosphoinositides (PPIns) are a family of phospholipids that are derived from phosphorylation of the parent molecule Phosphatidylinositol (PtdIns). The inositol head group can be reversibly phosphorylated on the 3, 4 or 5 positions to generate seven unique PPIns. Given the hydrophobicity of the diacylglycerol backbone and the hydrophilicity of the phosphorylated inositol headgroup, PPIns function as an interactive boundary between the membrane and the cytoplasm. Recruitment of PPIns modulating enzymes to specific subcellular compartments generates unique PPIns profiles, which in turn localise target proteins to maintain compartment identity and function [1,2,3]. PPIns regulate many cellular processes including membrane transport [2,4], ion channel function [5,6], cell adhesion, endo- and exo-cytosis [7], autophagy [8], transcription [1], RNA maturation [9] and cell survival [10] (Figure 1B).
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