OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation

Takashi Itoh, Eiko Kanno, Takefumi Uemura, Satoshi Waguri, Mitsunori Fukuda

    Research output: Contribution to journalArticlepeer-review

    113 Citations (Scopus)

    Abstract

    Macroautophagy is a bulk degradation system conserved in all eukaryotic cells. A ubiquitinlike protein, Atg8, and its homologues are essential for autophagosome formation and act as a landmark for selective autophagy of aggregated proteins and damaged organelles. In this study, we report evidence demonstrating that OATL1, a putative Rab guanosine triphosphatase - activating protein (GAP), is a novel binding partner of Atg8 homologues in mammalian cells. OATL1 is recruited to isolation membranes and autophagosomes through direct interaction with Atg8 homologues and is involved in the fusion between autophagosomes and lysosomes through its GAP activity. We further provide evidence that Rab33B, an Atg16L1-binding protein, is a target substrate of OATL1 and is involved in the fusion between autophagosomes and lysosomes, the same as OATL1. Because both its GAP activity and its Atg8 homologue - binding activity are required for OATL1 to function, we propose a model that OATL1 uses Atg8 homologues as a scaffold to exert its GAP activity and to regulate autophagosomal maturation.

    Original languageEnglish
    Pages (from-to)838-853
    Number of pages16
    JournalJournal of Cell Biology
    Volume192
    Issue number5
    DOIs
    Publication statusPublished - 2011 Mar 7

    ASJC Scopus subject areas

    • Cell Biology

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