Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains

Mol Cell. 1998 Jul;2(1):157-62. doi: 10.1016/s1097-2765(00)80125-2.

Abstract

Phosphoinositide 3-kinases (PI(3)K) are important regulators of receptor signaling cascades and intracellular membrane trafficking. To date, no protein domain has been identified that binds specifically to Ptdlns(3)P and thereby recruits/activates downstream effectors of Ptdlns(3)P signaling. Using an in vivo assay in yeast that detects Vps34 PI(3)K-dependent intracellular localization of a GFP reporter protein, and in vitro lipid-binding assays, we demonstrate that cysteine-rich RING domains of the FYVE finger subfamily bind specifically to Ptdlns phosphorylated exclusively at the D-3 position of the inositol ring. GFP-FYVE domain fusion proteins localized predominantly to membranes of endocytic compartments and required active Vps34 PI(3)K. Our data establish a molecular link between Vps34 PI(3)K and several FYVE domain-containing proteins (Vac1p, Vps27p) required for vacuolar/lysosomal protein trafficking.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Biological Transport
  • Cell Compartmentation
  • Fungal Proteins / physiology*
  • Genes, Reporter
  • Green Fluorescent Proteins
  • Liposomes
  • Luminescent Proteins / analysis
  • Lysosomes / metabolism
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphorylation
  • Protein Binding
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / ultrastructure
  • Signal Transduction / physiology*
  • Vacuoles / metabolism
  • Zinc Fingers / physiology*

Substances

  • Fungal Proteins
  • Liposomes
  • Luminescent Proteins
  • Phosphatidylinositol Phosphates
  • Recombinant Fusion Proteins
  • phosphatidylinositol 3-phosphate
  • Green Fluorescent Proteins
  • Phosphatidylinositol 3-Kinases