Abstract
Proteins essential for vesicle formation by the Coat Protein I (COPI) complex are being identified, but less is known about the role of specific lipids. Brefeldin-A ADP-ribosylated substrate (BARS) functions in the fission step of COPI vesicle formation. Here, we show that BARS induces membrane curvature in cooperation with phosphatidic acid. This finding has allowed us to further delineate COPI vesicle fission into two sub-stages: 1) an earlier stage of bud-neck constriction, in which BARS and other COPI components are required, and 2) a later stage of bud-neck scission, in which phosphatidic acid generated by phospholipase D2 (PLD2) is also required. Moreover, in contrast to the disruption of the Golgi seen on perturbing the core COPI components (such as coatomer), inhibition of PLD2 causes milder disruptions, suggesting that such COPI components have additional roles in maintaining Golgi structure other than through COPI vesicle formation.
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Acknowledgements
We thank Jian Li and Ming Bai for advice and discussions, and Richard Premont for technical assistance. This work was funded by grants from the NIH to V.W.H. (GM058615), M.A.F. (GM071520) and G.D. (GM071475), from Telethon (Italy), AIRC (Italy) to A.L. and A.M., and from the Canadian Institutes of Health Research (S.B.). H.G. was supported by a Marie Curie Fellowship.
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Experiments were performed mainly by J.S.Y., with help from H.D., S.Y.L., A.M., L.Z., G.V.B., C.V., G.T., A.N.B., G.D., G.B., A.G. and S.B. The project was planned mainly by V.W.H. with help from A.L. and M.A.H. All authors participated in data analysis.
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Supplementary Figures S1, S2, S3, S4, S5, S6, S7, S8, S9 and Supplementary Table 1 (PDF 1100 kb)
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Yang, JS., Gad, H., Lee, S. et al. A role for phosphatidic acid in COPI vesicle fission yields insights into Golgi maintenance. Nat Cell Biol 10, 1146–1153 (2008). https://doi.org/10.1038/ncb1774
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DOI: https://doi.org/10.1038/ncb1774
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