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PMID:18443221

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Citation

Hara, T, Takamura, A, Kishi, C, Iemura, S, Natsume, T, Guan, JL and Mizushima, N (2008) FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J. Cell Biol. 181:497-510

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.

Links

PubMed PMC2364687 Online version:10.1083/jcb.200712064

Keywords

Animals; Autophagy/physiology; 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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ULK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ESK9

F

Seeded From UniProt

complete

MOUSE:ULK1

located_in

GO:0034045: phagophore assembly site membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ULK1

involved_in

GO:0006914: autophagy

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ULK1

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:ULK1

involved_in

GO:0042594: response to starvation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RBCC1

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O70405

F

Seeded From UniProt

complete

MOUSE:RBCC1

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9QY01

F

Seeded From UniProt

complete

MOUSE:RBCC1

located_in

GO:0034045: phagophore assembly site membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RBCC1

involved_in

GO:0006914: autophagy

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ULK2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ESK9

F

Seeded From UniProt

complete

MOUSE:ULK2

located_in

GO:0034045: phagophore assembly site membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ULK2

enables

GO:0004674: protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:ULK2

involved_in

GO:0042594: response to starvation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ULK2

involved_in

GO:0006914: autophagy

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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