Cellular and Molecular Life Sciences

, Volume 67, Issue 23, pp 3927–3946 | Cite as

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

  • Katarzyna KwiatkowskaEmail author


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.


Plasma membrane Phosphatidylinositol 4,5-bisphosphate Type I phosphatidylinositol-4-phosphate 5-kinases Rac1 Talin AP-2 Lipid rafts 



Band 4.1-ezrin-radixin-moesin homology


Bruton’s tyrosine kinase




Diacylglycerol kinase


Epidermal growth factor


Inositol trisphosphate


Madin-Darby kidney cells


Myristoylated alanine-rich C kinase substrate


Growth-associated protein 43


Oculocerebrorenal syndrome of Lowe 1 phosphatase


Oxysterol-binding protein


Phosphatase and tensin homologue on chromosome 10


Phosphatidic acid




Phosphatidylinositol phosphate kinase


Phosphatidylinositol 3-kinase


Phosphatidylinositol 4-kinase


Phosphatidylinositol 3-monophosphate


Phosphatidylinositol 4-monophosphate


Phosphatidylinositol 5-monophosphate


Phosphatidylinositol 4,5-bishosphate


Phosphatidylinositol 3,4,5-trisphosphate


Phosphatidylinositol-4-phosphate adaptor protein

IPP 5-Ptase

Inositol polyphosphate 5-phosphatase


Phospholipase C


Phospholipase D




Pleckstrin homology


Type I phosphatidylinositol-4-phosphate 5-kinase


Type II phosphatidylinositol-5-phosphate 4-kinase


Yeast oxysterol-binding protein homologue



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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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  1. 1.Laboratory of Plasma Membrane ReceptorsNencki Institute of Experimental BiologyWarsawPoland

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