RRC ID 72403
Author Hara T, Takamura A, Kishi C, Iemura S, Natsume T, Guan JL, Mizushima N.
Title FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells.
Journal J Cell Biol
Abstract Autophagy is a membrane-mediated intracellular degradation system. The serine/threonine kinase Atg1 plays an essential role in autophagosome formation. However, the role of the mammalian Atg1 homologues UNC-51-like kinase (ULK) 1 and 2 are not yet well understood. We found that murine ULK1 and 2 localized to autophagic isolation membrane under starvation conditions. Kinase-dead alleles of ULK1 and 2 exerted a dominant-negative effect on autophagosome formation, suggesting that ULK kinase activity is important for autophagy. We next screened for ULK binding proteins and identified the focal adhesion kinase family interacting protein of 200 kD (FIP200), which regulates diverse cellular functions such as cell size, proliferation, and migration. We found that FIP200 was redistributed from the cytoplasm to the isolation membrane under starvation conditions. In FIP200-deficient cells, autophagy induction by various treatments was abolished, and both stability and phosphorylation of ULK1 were impaired. These results suggest that FIP200 is a novel mammalian autophagy factor that functions together with ULKs.
Volume 181(3)
Pages 497-510
Published 2008-5-5
DOI 10.1083/jcb.200712064
PII jcb.200712064
PMID 18443221
PMC PMC2364687
MeSH Animals Autophagy / physiology* Autophagy-Related Protein 5 Autophagy-Related Protein-1 Homolog Autophagy-Related Proteins Fibroblasts / cytology Fibroblasts / physiology Focal Adhesion Protein-Tyrosine Kinases / genetics Focal Adhesion Protein-Tyrosine Kinases / metabolism Fungal Proteins / genetics Fungal Proteins / metabolism Humans Intracellular Membranes / metabolism Intracellular Membranes / ultrastructure Mice Mice, Knockout Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism Phagosomes / metabolism* Protein Kinases / genetics Protein Kinases / metabolism Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism* Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism TOR Serine-Threonine Kinases
IF 8.811
DNA material pMXs-IP-EGFP-hFIP200 (RDB19623) pMXs-IP-EGFP-mAtg5 (RDB19634) p3xFLAG-CMV10-hFIP200 (RDB19762) pMXs-IP-EGFP-ULK1(K46N) (RDB19780) pMXs-IP-EGFP-LC3 (RDB19798)