FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells

Taichi Hara, Akito Takamura, Chieko Kishi, Shun Ichiro Iemura, Tohru Natsume, Jun Lin Guan, Noboru Mizushima

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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.

Original languageEnglish
Pages (from-to)497-510
Number of pages14
JournalJournal of Cell Biology
Volume181
Issue number3
DOIs
Publication statusPublished - 2008 May 5

ASJC Scopus subject areas

  • Cell Biology

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    Hara, T., Takamura, A., Kishi, C., Iemura, S. I., Natsume, T., Guan, J. L., & Mizushima, N. (2008). FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. Journal of Cell Biology, 181(3), 497-510. https://doi.org/10.1083/jcb.200712064