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.
Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes
These authors contributed equally to this work
Department of Bioregulation and Metabolism, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan
Anne Simonsen, Hanne C. G. Birkeland, David J. Gillooly, Noboru Mizushima, Akiko Kuma, Tamotsu Yoshimori, Thomas Slagsvold, Andreas Brech, Harald Stenmark; Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes. J Cell Sci 15 August 2004; 117 (18): 4239–4251. doi: https://doi.org/10.1242/jcs.01287
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