RRC ID 48778
Author Itoh T, Kanno E, Uemura T, Waguri S, Fukuda M.
Title OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation.
Journal J Cell Biol
Abstract Macroautophagy is a bulk degradation system conserved in all eukaryotic cells. A ubiquitin-like 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.
Volume 192(5)
Pages 839-53
Published 2011-3-7
DOI 10.1083/jcb.201008107
PII jcb.201008107
PMID 21383079
PMC PMC3051816
MeSH Amino Acid Sequence Animals Apoptosis Regulatory Proteins Autophagy / physiology* Autophagy-Related Protein 8 Family Carrier Proteins / analysis Carrier Proteins / metabolism Cell Line Cytoskeletal Proteins / analysis Cytoskeletal Proteins / metabolism GTPase-Activating Proteins / analysis GTPase-Activating Proteins / genetics GTPase-Activating Proteins / physiology* Green Fluorescent Proteins / analysis Intracellular Signaling Peptides and Proteins Lysosomes / physiology Membrane Proteins / analysis Membrane Proteins / metabolism Mice Microtubule-Associated Proteins / analysis Microtubule-Associated Proteins / metabolism Molecular Sequence Data Protein Interaction Mapping Recombinant Fusion Proteins / analysis rab GTP-Binding Proteins / metabolism
IF 8.811
Times Cited 99
DNA material pEF-T7-human TBC1D12 (RDB14978)