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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Autophagy / physiology*
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Autophagy-Related Proteins
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Chromosomes, Human, Pair 4
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Conserved Sequence
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Cytoplasmic Granules / metabolism
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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HeLa Cells
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Humans
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Intracellular Membranes / metabolism
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Intracellular Membranes / ultrastructure
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Macromolecular Substances / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / isolation & purification
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Membrane Proteins / metabolism*
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Microscopy, Electron, Transmission
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Molecular Sequence Data
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Nuclear Envelope / metabolism
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Nuclear Envelope / ultrastructure
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Phagosomes / metabolism*
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Phagosomes / ultrastructure
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Phosphoric Monoester Hydrolases / metabolism
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Proteasome Endopeptidase Complex / metabolism
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Protein Binding / physiology
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Protein Structure, Tertiary / physiology
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Protein Transport / physiology
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Transcription Factors / genetics
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Transcription Factors / isolation & purification
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Transcription Factors / metabolism*
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Ubiquitin / metabolism
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Zinc Fingers / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Autophagy-Related Proteins
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DNA, Complementary
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Macromolecular Substances
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Membrane Proteins
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Transcription Factors
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Ubiquitin
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WDFY3 protein, human
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Phosphoric Monoester Hydrolases
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phosphatidylinositol-3-phosphatase
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Proteasome Endopeptidase Complex