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Key components of the fission machinery are interchangeable

Nature Cell Biology volume 8, pages 1376–1382 (2006)Cite this article

Abstract

Brefeldin-A ADP-ribosylated substrate (BARS) and dynamin function in membrane fission in distinct intracellular transport pathways1, but whether their functions are mechanistically similar is unclear. Here, we show that ARFGAP1, a GTPase-activating protein (GAP) for ADP-ribosylation factor 1 (ARF1)2, couples to either BARS or endophilin B for vesicle formation by the coat protein I (COPI) complex — a finding that reveals an unanticipated mechanistic flexibility in mammalian COPI transport. Because dynamin is coupled to endophilin A in vesicle formation by the clathrin-coat complex3,4,5, our finding also predicts that dynamin and ARF GAPs are likely to be functional counterparts in membrane fission among different transport pathways that connect intracellular membrane compartments.

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Figure 1: MEFs do not require BARS for COPI-vesicle formation.
Figure 2: MEFs require endophilin B for COPI-vesicle formation.
Figure 3: COPI-vesicle formation requires either BARS or endophilin B depending on the cell type.
Figure 4: BARS and endophilin B act interchangeably in COPI vesicle reconstitution.
Figure 5: In vivo evidence for the interchangeability between BARS and endophilin B.

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Acknowledgements

We thank: J. Li and M. Bai for helpful discussions; and R. Premont, H, Kiener and H. Gilbert for technical assistance. This work was funded by grants from the National Institutes of Health to V.W.H., from Telethon (Italy) and the Italian Association for Cancer Research (AIRC) to A.L., and from the European Commission (postdoctoral fellowship programme) to H.G.

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Authors and Affiliations

  1. Division of Rheumatology, and Department of Medicine, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, MA, USA

    Jia-Shu Yang, Leiliang Zhang, Stella Y. Lee & Victor W. Hsu

  2. Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), 66030, Italy

    Helge Gad & Alberto Luini

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  1. Jia-Shu Yang
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Contributions

Experimental work was performed mainly by J.-S.Y. with help from L.Z., S.Y.L. and H.G. The project was planned mainly by V.W.H. with help from A.L. All authors participated in data analysis.

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Correspondence to Victor W. Hsu.

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Supplementary figures S1, S2 and S3 (PDF 624 kb)

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Yang, JS., Zhang, L., Lee, S. et al. Key components of the fission machinery are interchangeable. Nat Cell Biol 8, 1376–1382 (2006). https://doi.org/10.1038/ncb1503

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