Phosphatidylinositol(3)-phosphate signaling mediated by specific binding to RING FYVE domains.
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.
Howard Hughes Medical Institute, University of California, San Diego School of Medicine, La Jolla 92093-0668, USA.
C G
CG
Burd
S D
SD
Emr
D001665:Binding Sites; D001692:Biological Transport; D002451:Cell Compartmentation; D005656:Fungal Proteins / Q000502:physiology*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008081:Liposomes; D008164:Luminescent Proteins / Q000032:analysis; D008247:Lysosomes / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology*; D014617:Vacuoles / Q000378:metabolism; D016335:Zinc Fingers / Q000502:physiology*
D005656:Fungal Proteins; D049452:Green Fluorescent Proteins; D008081:Liposomes; D008164:Luminescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D011993:Recombinant Fusion Proteins; C055525:phosphatidylinositol 3-phosphate