PI4P and PI(4,5)P2 are essential but independent lipid determinants of membrane identity.
The quantitatively minor phospholipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P(2)] 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)P(2) 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)P(2). 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)P(2), which may be fulfilled by a more general polyanionic lipid requirement.
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK. gerald.hammond@nih.gov
Gerald R V
GR
Hammond
Michael J
MJ
Fischer
Karen E
KE
Anderson
Jon
J
Holdich
Ardita
A
Koteci
Tamas
T
Balla
Robin F
RF
Irvine
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004705:Endocytosis; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D000071228:Polyelectrolytes; D011108:Polymers; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D055672:Static Electricity; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099182:Phosphoinositide 5-Phosphatases
D008565:Membrane Proteins; D010446:Peptide Fragments; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010744:Phosphoric Monoester Hydrolases; D000071228:Polyelectrolytes; D011108:Polymers; D043643:Receptor, Muscarinic M1; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D050916:TRPV Cation Channels; D000099182:Phosphoinositide 5-Phosphatases; C494482:TRPV1 protein, human; C037178:phosphatidylinositol 4-phosphate; C081864:SAC1 protein, S cerevisiae