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COPI acts in both vesicular and tubular transport

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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Figure 1: LPAAT activity promotes COPI vesicle formation and inhibits tubule formation from Golgi membrane.
Figure 2: PLA2 activity inhibits COPI vesicle formation and promotes tubule formation.
Figure 3: The relative roles of COPI and lipid enzymes in vesicle versus tubule formation.
Figure 4: Characterizing how COPI acts in Golgi structure and transport.
Figure 5: Characterizing cargo transport in COPI tubules.

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References

  1. Cai, H., Reinisch, K. & Ferro-Novick, S. Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev. Cell 12, 671–682 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Pucadyil, T. J. & Schmid, S. L. Conserved functions of membrane active GTPases in coated vesicle formation. Science 325, 1217–1220 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bard, F. & Malhotra, V. The formation of TGN-to-plasma-membrane transport carriers. Annu. Rev. Cell Dev. Biol. 22, 439–455 (2006).

    Article  CAS  PubMed  Google Scholar 

  4. De Matteis, M. A. & Luini, A. Exiting the Golgi complex. Nat. Rev. Mol. Cell Biol. 9, 273–284 (2008).

    Article  CAS  PubMed  Google Scholar 

  5. Hsu, V. W., Lee, S. Y. & Yang, J. S. The evolving understanding of COPI vesicle formation. Nat. Rev. Mol. Cell Biol. 10, 360–364 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. Waters, M. G., Serafini, T. & Rothman, J. E. ‘Coatomer’: a cytosolic protein complex containing subunits of non-clathrin-coated Golgi transport vesicles. Nature 349, 248–251 (1991).

    Article  CAS  PubMed  Google Scholar 

  7. Donaldson, J. G., Cassel, D., Kahn, R. A. & Klausner, R. D. ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein β-COP to Golgi membranes. Proc. Natl Acad. Sci. USA 89, 6408–6412 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cukierman, E., Huber, I., Rotman, M. & Cassel, D. The ARF1-GTPase-activating protein: zinc finger motif and Golgi complex localization. Science 270, 1999–2002 (1995).

    Article  CAS  PubMed  Google Scholar 

  9. Yang, J. S. et al. ARFGAP1 promotes the formation of COPI vesicles, suggesting function as a component of the coat. J. Cell Biol. 159, 69–78 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lee, S. Y., Yang, J. S., Hong, W., Premont, R. T. & Hsu, V. W. ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation. J. Cell Biol. 168, 281–290 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yang, J. S. et al. A role for BARS at the fission step of COPI vesicle formation from Golgi membrane. EMBO J. 24, 4133–4143 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Weigert, R. et al. CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid. Nature 402, 429–433 (1999).

    Article  CAS  PubMed  Google Scholar 

  13. Gallop, J. L., Butler, P. J. & McMahon, H. T. Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission. Nature 438, 675–678 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Yang, J. S. et al. A role for phosphatidic acid in COPI vesicle fission yields insights into Golgi maintenance. Nat. Cell Biol. 10, 1146–1153 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chambers, K., Judson, B. & Brown, W. J. A unique lysophospholipid acyltransferase (LPAT) antagonist, CI-976, affects secretory and endocytic membrane trafficking pathways. J. Cell Sci. 118, 3061–3071 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Shindou, H. & Shimizu, T. Acyl-CoA:lysophospholipid acyltransferases. J. Biol. Chem. 284, 1–5 (2009).

    Article  CAS  PubMed  Google Scholar 

  17. Schmidt, J. A. & Brown, W. J. Lysophosphatidic acid acyltransferase 3 regulates Golgi complex structure and function. J. Cell Biol. 186, 211–218 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yang, J. S. et al. Key components of the fission machinery are interchangeable. Nat. Cell Biol. 8, 1376–1382 (2006).

    CAS  PubMed  Google Scholar 

  19. Schaloske, R. H. & Dennis, E. A. The phospholipase A2 superfamily and its group numbering system. Biochim. Biophys. Acta 1761, 1246–1259 (2006).

    Article  CAS  PubMed  Google Scholar 

  20. Evans, J. H., Spencer, D. M., Zweifach, A. & Leslie, C. C. Intracellular calcium signals regulating cytosolic phospholipase A2 translocation to internal membranes. J. Biol. Chem. 276, 30150–30160 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Asp, L. et al. Early stages of Golgi vesicle and tubule formation require diacylglycerol. Mol. Biol. Cell 20, 780–790 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. San Pietro, E. et al. Group IV phospholipase A(2)α controls the formation of inter-cisternal continuities involved in intra-golgi transport. PLoS Biol. 7, e1000194 (2009).

    Article  PubMed  Google Scholar 

  23. Guo, Q., Vasile, E. & Krieger, M. Disruptions in Golgi structure and membrane traffic in a conditional lethal mammalian cell mutant are corrected by ε-COP. J. Cell Biol. 125, 1213–1224 (1994).

    Article  CAS  PubMed  Google Scholar 

  24. Dall’Armi, C. et al. The phospholipase D1 pathway modulates macroautophagy. Nat. Commun. 1, 142 (2010).

    Article  PubMed  Google Scholar 

  25. Oliveira, T. G. et al. Phospholipase d2 ablation ameliorates Alzheimer’s disease-linked synaptic dysfunction and cognitive deficits. J. Neurosci. 30, 16419–16428 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lavieri, R. et al. Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part II. Identification of the 1,3,8-triazaspiro[4,5]decan-4-one privileged structure that engenders PLD2 selectivity. Bioorg. Med. Chem. Lett. 19, 2240–2243 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lewis, J. A. et al. Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: impact of alternative halogenated privileged structures for PLD1 specificity. Bioorg. Med. Chem. Lett. 19, 1916–1920 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Emr, S. et al. Journeys through the Golgi–taking stock in a new era. J. Cell Biol. 187, 449–453 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Glick, B. S. & Nakano, A. Membrane traffic within the Golgi apparatus. Annu. Rev. Cell Dev. Biol. 25, 113–132 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. de Carvalho, M. G. et al. Identification of phosphorylation sites of human 85-kDa cytosolic phospholipase A2 expressed in insect cells and present in human monocytes. J. Biol. Chem. 271, 6987–6997 (1996).

    Article  CAS  PubMed  Google Scholar 

  31. Yuki, K., Shindou, H., Hishikawa, D. & Shimizu, T. Characterization of mouse lysophosphatidic acid acyltransferase 3: an enzyme with dual functions in the testis. J. Lipid Res. 50, 860–869 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Palmer, D. J., Helms, J. B., Beckers, C. J., Orci, L. & Rothman, J. E. Binding of coatomer to Golgi membranes requires ADP-ribosylation factor. J. Biol. Chem. 268, 12083–12089 (1993).

    CAS  PubMed  Google Scholar 

  33. Kweon, H. S. et al. Golgi enzymes are enriched in perforated zones of golgi cisternae but are depleted in COPI vesicles. Mol. Biol. Cell 15, 4710–4724 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bonazzi, M. et al. CtBP3/BARS drives membrane fission in dynamin-independent transport pathways. Nat. Cell Biol. 7, 570–580 (2005).

    Article  CAS  PubMed  Google Scholar 

  35. Siegrist, M. S. et al. Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition. Proc. Natl Acad. Sci. USA 106, 18792–18797 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bollinger, J. G., Ii, H., Sadilek, M. & Gelb, M. H. Improved method for the quantification of lysophospholipids including enol ether species by liquid chromatography–tandem mass spectrometry. J. Lipid Res. 51, 440–447 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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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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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.

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Correspondence to Alberto Luini or Victor W. Hsu.

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Yang, JS., Valente, C., Polishchuk, R. et al. COPI acts in both vesicular and tubular transport. Nat Cell Biol 13, 996–1003 (2011). https://doi.org/10.1038/ncb2273

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