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One lipid, multiple functions: how various pools of PI(4,5)P2 are created in the plasma membrane

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Abstract

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor lipid of the inner leaflet of the plasma membrane that controls the activity of numerous proteins and serves as a source of second messengers. This multifunctionality of PI(4,5)P2 relies on mechanisms ensuring transient appearance of PI(4,5)P2 clusters in the plasma membrane. One such mechanism involves phosphorylation of PI(4)P to PI(4,5)P2 by the type I phosphatidylinositol-4-phosphate 5-kinases (PIP5KI) at discrete membrane locations coupled with PI(4)P delivery/synthesis at the plasma membrane. Simultaneously, both PI(4)P and PI(4,5)P2 participate in anchoring PIP5KI at the plasma membrane via electrostatic bonds. PIP5KI isoforms are also selectively recruited and activated at the plasma membrane by Rac1, talin, or AP-2 to generate PI(4,5)P2 in ruffles and lamellipodia, focal contacts, and clathrin-coated pits. In addition, PI(4,5)P2 can accumulate at sphingolipid/cholesterol-based rafts following activation of distinct membrane receptors or be sequestered in a reversible manner due to electrostatic constrains posed by proteins like MARCKS.

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Abbreviations

FERM:

Band 4.1-ezrin-radixin-moesin homology

BTK:

Bruton’s tyrosine kinase

DAG:

Diacylglycerol

DAGK:

Diacylglycerol kinase

EGF:

Epidermal growth factor

IP3 :

Inositol trisphosphate

MDCK:

Madin-Darby kidney cells

MARCKS:

Myristoylated alanine-rich C kinase substrate

GAP43:

Growth-associated protein 43

OCRL1:

Oculocerebrorenal syndrome of Lowe 1 phosphatase

OSBP:

Oxysterol-binding protein

PTEN:

Phosphatase and tensin homologue on chromosome 10

PA:

Phosphatidic acid

PI:

Phosphatidylinositol

PIPK:

Phosphatidylinositol phosphate kinase

PI3K:

Phosphatidylinositol 3-kinase

PI4K:

Phosphatidylinositol 4-kinase

PI(3)P:

Phosphatidylinositol 3-monophosphate

PI(4)P:

Phosphatidylinositol 4-monophosphate

PI(5)P:

Phosphatidylinositol 5-monophosphate

PI(4,5)P2 :

Phosphatidylinositol 4,5-bishosphate

PI(3,4,5)P3 :

Phosphatidylinositol 3,4,5-trisphosphate

Fapp:

Phosphatidylinositol-4-phosphate adaptor protein

IPP 5-Ptase:

Inositol polyphosphate 5-phosphatase

PLC:

Phospholipase C

PLD:

Phospholipase D

PTB:

Phosphotyrosine-binding

PH:

Pleckstrin homology

PIP5KI:

Type I phosphatidylinositol-4-phosphate 5-kinase

PIP4KII:

Type II phosphatidylinositol-5-phosphate 4-kinase

OSH2:

Yeast oxysterol-binding protein homologue

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Acknowledgments

I gratefully thank Prof. Andrzej Sobota, Nencki Institute of Experimental Biology, Warsaw, for support and excellent discussion. I also thank Prof. Jan Fronk, Warsaw University, for valuable comments on the manuscript.

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  1. Laboratory of Plasma Membrane Receptors, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093, Warsaw, Poland

    Katarzyna Kwiatkowska

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Kwiatkowska, K. One lipid, multiple functions: how various pools of PI(4,5)P2 are created in the plasma membrane. Cell. Mol. Life Sci. 67, 3927–3946 (2010). https://doi.org/10.1007/s00018-010-0432-5

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