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.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Simonsen A,Birkeland HC,Gillooly DJ,Mizushima N,Kuma A,Yoshimori T,Slagsvold T,Brech A,Stenmark Hdoi
10.1242/jcs.01287keywords:
subject
Has Abstractpub_date
2004-08-15 00:00:00pages
4239-51issue
Pt 18eissn
0021-9533issn
1477-9137pii
jcs.01287journal_volume
117pub_type
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