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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 RIS Download

Mesh terms: Animals | Cell Membrane | Electroporation | Female | Fibroblasts | Genetic Vectors | HeLa Cells | Humans | Male | Mice | Mice, 129 Strain | Mice, Inbred C57BL | Mice, Knockout | Minor Histocompatibility Antigens | Phosphatidylinositol Phosphates | Phosphotransferases (Alcohol Group Acceptor) | Up-Regulation

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Associated grants

  • Agency: NIGMS NIH HHS, Id: T32 GM007223
  • Agency: NIDDK NIH HHS, Id: DK075772
  • Agency: NIDDK NIH HHS, Id: K01 DK078625
  • Agency: NIDDK NIH HHS, Id: R01 DK075772
  • Agency: NIDA NIH HHS, Id: P30 DA018343
  • Agency: NIDDK NIH HHS, Id: DK45735
  • Agency: NIDDK NIH HHS, Id: R01 DK082700
  • Agency: NIDDK NIH HHS, Id: P30 DK045735
  • Agency: NIDDK NIH HHS, Id: DK078625
  • Agency: NIDA NIH HHS, Id: DA018343
  • Agency: NIDDK NIH HHS, Id: DK082700
  • Agency: NIGMS NIH HHS, Id: T32GM007223
  • Agency: NINDS NIH HHS, Id: R37NS036251
  • Agency: NINDS NIH HHS, Id: R37 NS036251

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GenBank

NIH genetic sequence database that provides an annotated collection of all publicly available DNA sequences for almost 280 000 formally described species. (Jan 2014) These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of the International Nucleotide Sequence Database Collaboration and daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP.

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