Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase

Sabina Tahirovic, Markus Schorr, Peter Mayinger

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Phosphatidylinositol 4-phosphate (Ptdlns(4)P) regulates diverse cellular processes, such as actin cytoskeletal organization, Golgi trafficking and vacuolar biogenesis. Synthesis and turnover of Ptdlns(4)P is mediated by a set of specific lipid kinases and phosphatases. Here we show that the polyphosphoinositide phosphatase Sac1p has a central role in compartment-specific regulation of Ptdlns(4)P. We have found that sac1Δ mutants show pleiotropic, synthetically lethal interactions with mutations in genes required for vacuolar protein sorting (Vps). Disruption of the SAC1 gene also caused a defect in the late endocytic pathway. These trafficking phenotypes correlated with a dramatic accumulation of Ptdlns(4)P at vacuolar membranes. In addition, sac1 mutants displayed elevated endoplasmic reticulum Ptdlns(4)P. The accumulation of Ptdlns(4)P at the endoplasmic reticulum and vacuole and the endocytic defect could be compensated by mutations in the Ptdlns 4-kinase Stt4p. Our results indicate that elimination of Sac1p causes accumulation of a Stt4p-specific Ptdlns(4)P pool at internal membranes which impairs late endocytic and vacuolar trafficking. We conclude that Sac1p functions in confining Ptdlns(4)P-dependent processes to specific intracellular membranes.

Original languageEnglish (US)
Pages (from-to)116-130
Number of pages15
JournalTraffic
Volume6
Issue number2
DOIs
StatePublished - Feb 2005

Fingerprint

Phosphoric Monoester Hydrolases
Lipids
Membranes
Endoplasmic Reticulum
Phosphotransferases
Genes
Intracellular Membranes
Defects
Mutation
Protein Transport
Vacuoles
Sorting
phosphatidylinositol 4-phosphate
Actins
Phenotype
Proteins

Keywords

  • Endoplasmic reticulum
  • Endosomes
  • Lipid phosphatase
  • Phosphoinositides
  • Sac1p
  • Vacuole

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Structural Biology
  • Molecular Biology
  • Genetics

Cite this

Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase. / Tahirovic, Sabina; Schorr, Markus; Mayinger, Peter.

In: Traffic, Vol. 6, No. 2, 02.2005, p. 116-130.

Research output: Contribution to journalArticle

Tahirovic, Sabina ; Schorr, Markus ; Mayinger, Peter. / Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase. In: Traffic. 2005 ; Vol. 6, No. 2. pp. 116-130.
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