TY - JOUR
T1 - OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation
AU - Itoh, Takashi
AU - Kanno, Eiko
AU - Uemura, Takefumi
AU - Waguri, Satoshi
AU - Fukuda, Mitsunori
PY - 2011/3/7
Y1 - 2011/3/7
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201008107
DO - 10.1083/jcb.201008107
M3 - Article
C2 - 21383079
AN - SCOPUS:79952422876
VL - 192
SP - 838
EP - 853
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 5
ER -