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PtdIns4P synthesis by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity.

Plasma membrane phosphatidylinositol (PI) 4-phosphate (PtdIns4P) has critical functions via both direct interactions and metabolic conversion to PI 4,5-bisphosphate (PtdIns(4,5)P₂) and other downstream metabolites. However, mechanisms that control this PtdIns4P pool in cells of higher eukaryotes remain elusive. PI4KIIIα, the enzyme thought to synthesize this PtdIns4P pool, is reported to localize in the ER, contrary to the plasma membrane localization of its yeast homologue, Stt4. In this paper, we show that PI4KIIIα was targeted to the plasma membrane as part of an evolutionarily conserved complex containing Efr3/rolling blackout, which we found was a palmitoylated peripheral membrane protein. PI4KIIIα knockout cells exhibited a profound reduction of plasma membrane PtdIns4P but surprisingly only a modest reduction of PtdIns(4,5)P₂ because of robust up-regulation of PtdIns4P 5-kinases. In these cells, however, much of the PtdIns(4,5)P₂ was localized intracellularly, rather than at the plasma membrane as in control cells, along with proteins typically restricted to this membrane, revealing a major contribution of PI4KIIIα to the definition of plasma membrane identity.

Pubmed ID: 23229899


  • Nakatsu F
  • Baskin JM
  • Chung J
  • Tanner LB
  • Shui G
  • Lee SY
  • Pirruccello M
  • Hao M
  • Ingolia NT
  • Wenk MR
  • De Camilli P


The Journal of cell biology

Publication Data

December 10, 2012

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA018343
  • Agency: NIDDK NIH HHS, Id: DK075772
  • Agency: NIDDK NIH HHS, Id: DK078625
  • Agency: NIDDK NIH HHS, Id: DK082700
  • Agency: NIDDK NIH HHS, Id: DK45735
  • Agency: NIDA NIH HHS, Id: P30 DA018343
  • Agency: NIDDK NIH HHS, Id: R01 DK082700
  • Agency: NINDS NIH HHS, Id: R37 NS036251
  • Agency: NINDS NIH HHS, Id: R37NS036251
  • Agency: NIGMS NIH HHS, Id: T32 GM007223
  • Agency: NIGMS NIH HHS, Id: T32GM007223

Mesh Terms

  • Animals
  • Cell Membrane
  • Electroporation
  • Female
  • Fibroblasts
  • Genetic Vectors
  • HeLa Cells
  • Humans
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphatidylinositol Phosphates
  • Phosphotransferases (Alcohol Group Acceptor)
  • Up-Regulation