Abstract

Intracellular transport occurs through two general types of carrier, either vesicles1,2 or tubules3,4. Coat proteins act as the core machinery that initiates vesicle formation1,2, but the counterpart that initiates tubule formation has been unclear. Here, we find that the coat protein I (COPI) complex initially drives the formation of Golgi buds. Subsequently, a set of opposing lipid enzymatic activities determines whether these buds become vesicles or tubules. Lysophosphatidic acid acyltransferase-γ (LPAATγ) promotes COPI vesicle fission for retrograde vesicular transport. In contrast, cytosolic phospholipase A2-α (cPLA2α) inhibits this fission event to induce COPI tubules, which act in anterograde intra-Golgi transport and Golgi ribbon formation. These findings not only advance a molecular understanding of how COPI vesicle fission is achieved, but also provide insight into how COPI acts in intra-Golgi transport and reveal an unexpected mechanistic relationship between vesicular and tubular transport.

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Acknowledgements

We thank J. Li and M. Bai for advice and discussions, G. Di Tullio and M. Santoro for generating the anti-LPAATγ antibody, and R. Loper for technical assistance. This work is financially supported by grants from the National Institutes of Health to V.W.H. (GM058615), D.B.M. (AI071155 and AR048632), C.C.L. (HL061378), M.H.G. (HL050040) and W.J.B. (GM051596), and also by grants from Telethon to A.L. (GGPO823) and R.S.P. (GTF08001), from AIRC to A.L. (IG4700), D.C. (IG4664) and R.P. (IG10233), and from European Grant Eucilia to A.L. (HEALT-F2-2007-201804). C.V. is a recipient of an Italian Foundation for Cancer Research Fellowship. D.B.M. is supported by the Burroughs Wellcome Fund Program in Translational Medicine.

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Affiliations

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

    • Jia-Shu Yang
    • , Emilie Layre
    • , D. Branch Moody
    •  & Victor W. Hsu
  2. Telethon Institute of Genetics and Medicine, Via Pietro Castellino 111, 80131 Napoli, Italy

    • Carmen Valente
    • , Roman S. Polishchuk
    •  & Alberto Luini
  3. Institute of Protein Biochemistry, National Research Council, Via Pietro Castellino 111, 80131 Napoli, Italy

    • Carmen Valente
    • , Gabriele Turacchio
    • , Daniela Corda
    •  & Alberto Luini
  4. Department of Pediatrics, National Jewish Health, and Departments of Pathology and Pharmacology, University of Colorado School of Medicine, Denver, Colorado 80262, USA

    • Christina C. Leslie
  5. Department of Chemistry and Biochemistry, University of Washington, Seattle, Washington 98195, USA

    • Michael H. Gelb
  6. Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA

    • William J. Brown

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Contributions

J-S.Y., C.V., R.S.P., G.T., E.L., C.C.L., M.H.G. and W.J.B participated in experimental work and data analysis. V.W.H., A.L., D.B.M. and D.C. participated in project planning and data analysis. V.W.H., A.L. and J-S.Y. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Alberto Luini or Victor W. Hsu.

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DOI

https://doi.org/10.1038/ncb2273

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