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Science 337 (6095): 727-730

Copyright © 2012 by the American Association for the Advancement of Science

PI4P and PI(4,5)P2 Are Essential But Independent Lipid Determinants of Membrane Identity

Gerald R. V. Hammond,1,3,* Michael J. Fischer,1 Karen E. Anderson,2 Jon Holdich,1 Ardita Koteci,1 Tamas Balla,3 Robin F. Irvine1,*

Abstract: The quantitatively minor phospholipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] fulfills many cellular functions in the plasma membrane (PM), whereas its synthetic precursor, phosphatidylinositol 4-phosphate (PI4P), has no assigned PM roles apart from PI(4,5)P2 synthesis. We used a combination of pharmacological and chemical genetic approaches to probe the function of PM PI4P, most of which was not required for the synthesis or functions of PI(4,5)P2. However, depletion of both lipids was required to prevent PM targeting of proteins that interact with acidic lipids or activation of the transient receptor potential vanilloid 1 cation channel. Therefore, PI4P contributes to the pool of polyanionic lipids that define plasma membrane identity and to some functions previously attributed specifically to PI(4,5)P2, which may be fulfilled by a more general polyanionic lipid requirement.

1 Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.
2 Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
3 Section on Molecular Signal Transduction, Program for Developmental Neuroscience, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA

* To whom correspondence should be addressed. E-mail: gerald.hammond{at}nih.gov (G.R.V.H.) or rfi20{at}cam.ac.uk (R.F.I.)

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