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Features of the Phosphatidylinositol Cycle and its Role in Signal Transduction

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Abstract

The phosphatidylinositol cycle (PI-cycle) has a central role in cell signaling. It is the major pathway for the synthesis of phosphatidylinositol and its phosphorylated forms. In addition, some lipid intermediates of the PI-cycle, including diacylglycerol and phosphatidic acid, are also important lipid signaling agents. The PI-cycle has some features that are important for the understanding of its role in the cell. As a cycle, the intermediates will be regenerated. The PI-cycle requires a large amount of metabolic energy. There are different steps of the cycle that occur in two different membranes, the plasma membrane and the endoplasmic reticulum. In order to complete the PI-cycle lipid must be transferred between the two membranes. The role of the Nir proteins in the process has recently been elucidated. The lipid intermediates of the PI-cycle are normally highly enriched with 1-stearoyl-2-arachidonoyl molecular species in mammals. This enrichment will be retained as long as the intermediates are segregated from other lipids of the cell. However, there is a significant fraction (>15 %) of lipids in the PI-cycle of normal cells that have other acyl chains. Phosphatidylinositol largely devoid of arachidonoyl chains are found in cancer cells. Phosphatidylinositol species with less unsaturation will not be as readily converted to phosphatidylinositol-3,4,5-trisphosphate, the lipid required for the activation of Akt with resulting effects on cell proliferation. Thus, the cyclical nature of the PI-cycle, its dependence on acyl chain composition and its requirement for lipid transfer between two membranes, explain many of the biological properties of this cycle.

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Fig. 1
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Taken from English and Voeltz (2013) (Color figure online)

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Abbreviations

CDP-DAG:

Cytidine diphosphate-diacylglycerol

CDS:

CDP-DAG synthase (Phosphatidate cytidylyltransferase)

DAG:

Diacylglycerol

DGK:

Diacylglycerol kinase

LPIAT1:

Lysophosphatidylinositol acyltransferase 1 (O-acyltransferase containing domain 7) (MBOAT7)

PA:

Phosphatidic acid

PI:

Phosphatidylinositol

PI-cycle:

Phosphatidylinositol cycle

PI3K:

Phosphatidylinositol-4,5-bisphosphate 3-kinase

PI4K:

Phosphatidylinositol-4-kinase

PI4P:

Phosphatidylinositol-4-phosphate

PIP2 :

Phosphatidylinositol-4,5-bisphosphate

PIP3 :

Phosphatidylinositol-3,4,5-trisphosphate

PIP n :

Phosphorylated forms of PI

PI4P5K:

Phosphatidylinositol-4-phosphate 5-kinase

PIS:

PI synthase (CDP-diacylglycerol-inositol 3-phosphatidyltransferase)

PKC:

Protein kinase C

PLC:

Phospholipase C (1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase)

PLD:

Phospholipase D

PTEN:

Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (Phosphatase and tensin homolog)

TrpC channel:

Transient receptor cation channel

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Acknowledgments

This work was supported by the Natural Sciences and Engineering Council of Canada, Grant 9848.

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  1. Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada

    Richard M. Epand

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Epand, R.M. Features of the Phosphatidylinositol Cycle and its Role in Signal Transduction. J Membrane Biol 250, 353–366 (2017). https://doi.org/10.1007/s00232-016-9909-y

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  • DOI: https://doi.org/10.1007/s00232-016-9909-y

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