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CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid

Nature volume 402, pages 429–433 (1999)Cite this article

Abstract

Membrane fission is essential in intracellular transport. Acyl-coenzyme As (acyl-CoAs) are important in lipid remodelling and are required for fission of COPI-coated vesicles1. Here we show that CtBP/BARS, a protein that functions in the dynamics of Golgi tubules2, is an essential component of the fission machinery operating at Golgi tubular networks, including Golgi compartments involved in protein transport and sorting. CtBP/BARS-induced fission was preceded by the formation of constricted sites in Golgi tubules, whose extreme curvature is likely to involve local changes in the membrane lipid composition. We find that CtBP/BARS uses acyl-CoA to selectively catalyse the acylation of lysophosphatidic acid to phosphatidic acid both in pure lipidic systems and in Golgi membranes, and that this reaction is essential for fission. Our results indicate a key role for lipid metabolic pathways in membrane fission.

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Figure 1: CtBP/BARS induces fission of the Golgi tubular network (negative staining).
Figure 2: Structure of CtBP/BARS-induced fission intermediates in Golgi tubules.
Figure 3: Acyl-CoAs are essential cofactors for CtBP/BARS-induced fission/fragmentation of Golgi tubular networks.
Figure 4: Acyl-CoAs support CtBP/BARS-dependent LPA acyltransferase and fission of Golgi membranes.
Figure 5: PA synthesis in Golgi membranes is associated with membrane fission/fragmentation.

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Acknowledgements

We thank A. Mironov Jr, G. Beznoussenko and R. Polishchuk for help with the electron microscopy; V. Malhotra for helpful discussions; C. P. Berrie for critical reading of the text; C. Iurisci for technical assistance; J. Füllekrug, K. Moremen, M. Zerial, G. Banting, A. Hubbard, E. Sztul, H. P. Hauri and V. Malhotra for their generous gifts of antibodies. This work was supported in part by grants from Telethon-Italy, AIRC, and CNR-Progetti Singoli e Finalizzato “Biotecnologie”. S.S. and R.M. are recipients of FIRC fellowships.

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  1. Roberto Weigert, Maria Giuseppina Silletta and Koert N. J. Burger: These authors contributed equally to this paper

Authors and Affiliations

  1. Department of Cell Biology and Oncology, Istituto di Ricerche Farmacologiche “Mario Negri”, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), 66030, Italy

    Roberto Weigert, Maria Giuseppina Silletta, Stefania Spanò, Gabriele Turacchio, Claudia Cericola, Antonino Colanzi, Silvia Senatore, Raffaella Mancini, Elena V. Polishchuk, Francesco Facchiano, Alexander Mironov, Alberto Luini & Daniela Corda

  2. Department of Biochemistry and Molecular Pharmacology, Istituto di Ricerche Farmacologiche “Mario Negri”, Milano, 20157, Italy

    Mario Salmona

  3. Laboratory of Vascular Pathology, Istituto Dermopatico dell' Immacolata, Rome, Italy

    Francesco Facchiano

  4. Department of Biochemistry of Membranes, Institute of Biomembranes, Utrecht University, CH Utrecht, 3584, The Netherlands

    Koert N. J. Burger

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Correspondence to Alberto Luini.

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Weigert, R., Silletta, M., Spanò, S. et al. CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid. Nature 402, 429–433 (1999). https://doi.org/10.1038/46587

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