Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors

EMBO J. 2004 May 5;23(9):1922-33. doi: 10.1038/sj.emboj.7600203. Epub 2004 Apr 22.

Abstract

Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), made by Fab1p, is essential for vesicle recycling from vacuole/lysosomal compartments and for protein sorting into multivesicular bodies. To isolate PtdIns(3,5)P2 effectors, we identified Saccharomyces cerevisiae mutants that display fab1delta-like vacuole enlargement, one of which lacked the SVP1/YFR021w/ATG18 gene. Expressed Svp1p displays PtdIns(3,5)P2 binding of exquisite specificity, GFP-Svp1p localises to the vacuole membrane in a Fab1p-dependent manner, and svp1delta cells fail to recycle a marker protein from the vacuole to the Golgi. Cells lacking Svp1p accumulate abnormally large amounts of PtdIns(3,5)P2. These observations identify Svp1p as a PtdIns(3,5)P2 effector required for PtdIns(3,5)P2-dependent membrane recycling from the vacuole. Other Svp1p-related proteins, including human and Drosophila homologues, bind PtdIns(3,5)P2 similarly. Svp1p and related proteins almost certainly fold as beta-propellers, and the PtdIns(3,5)P2-binding site is on the beta-propeller. It is likely that many of the Svp1p-related proteins that are ubiquitous throughout the eukaryotes are PtdIns(3,5)P2 effectors. Svp1p is not involved in the contributions of FAB1/PtdIns(3,5)P2 to MVB sorting or to vacuole acidification and so additional PtdIns(3,5)P2 effectors must exist.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Autophagy-Related Proteins
  • Base Sequence
  • Cloning, Molecular
  • Endosomes / metabolism*
  • Escherichia coli
  • Gene Components
  • Genetic Vectors
  • Green Fluorescent Proteins / metabolism
  • Membrane Proteins
  • Molecular Sequence Data
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Plasmids / genetics
  • Protein Binding
  • Protein Folding
  • Protein Transport / physiology
  • Rhinovirus
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Vacuoles / metabolism*

Substances

  • ATG18 protein, S cerevisiae
  • Autophagy-Related Proteins
  • Membrane Proteins
  • Phosphatidylinositol Phosphates
  • Saccharomyces cerevisiae Proteins
  • phosphatidylinositol 3,5-diphosphate
  • Green Fluorescent Proteins
  • FAB1 protein, S cerevisiae
  • Phosphotransferases (Alcohol Group Acceptor)