Authors: Simonsen A; Birkeland HC; Gillooly DJ; Mizushima N; Kuma A; Yoshimori T; Slagsvold T; Brech A; Stenmark H
Abstract: Phosphatidylinositol-3-phosphate [PtdIns(3)P] regulates endocytic and autophagic membrane traffic. In order to understand the downstream effects of PtdIns(3)P in these processes, it is important to identify PtdIns(3)P-binding proteins, many of which contain FYVE zinc-finger domains. Here, we describe a novel giant FYVE-domain-containing protein, named autophagy-linked FYVE protein (Alfy). Alfy is ubiquitously expressed, shares sequence similarity with the Chediak-Higashi-syndrome protein and has putative homologues in flies, nematodes and fission yeast. Alfy binds PtdIns(3)P in vitro and partially colocalizes with PtdIns(3)P in vivo. Unlike most other FYVE-domain proteins, Alfy is not found on endosomes but instead localizes mainly to the nuclear envelope. When HeLa cells are starved or treated with a proteasome inhibitor, Alfy relocalizes to characteristic filamentous cytoplasmic structures located close to autophagic membranes and ubiquitin-containing protein aggregates. By electron microscopy, similar structures can be found within autophagosomes. We propose that Alfy might target cytosolic protein aggregates for autophagic degradation.
Keywords: Autophagy/*physiology; Chromosomes, Human, Pair 4; Conserved Sequence; Cytoplasmic Granules/metabolism; DNA, Complementary/analysis/genetics; HeLa Cells; Humans; Intracellular Membranes/metabolism/ultrastructure; Macromolecular Substances/metabolism; Membrane Proteins/genetics/isolation & purification/*metabolism; Microscopy, Electron, Transmission; Molecular Sequence Data; Nuclear Envelope/metabolism/ultrastructure; Phagosomes/*metabolism/ultrastructure; Phosphoric Monoester Hydrolases/metabolism; Proteasome Endopeptidase Complex/metabolism; Protein Binding/physiology; Protein Structure, Tertiary/physiology; Protein Transport/physiology; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Transcription Factors/genetics/isolation & purification/*metabolism; Ubiquitin/metabolism; Zinc Fingers/physiology|
Journal: Journal of cell science Volume: 117 Issue: Pt 18 Pages: 4239-51 Date: Aug. 5, 2004 PMID: 15292400 |
Simonsen A, Birkeland HC, Gillooly DJ, Mizushima N, Kuma A, Yoshimori T, Slagsvold T, Brech A, Stenmark H (2004) Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes. Journal of cell science 117: 4239-51.
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