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The Lysophospholipid Acyltransferase Antagonist CI-976 Inhibits a Late Step in COPII Vesicle Budding

  1. William J. Brown1,*,
  2. Helen Plutner2,
  3. Daniel Drecktrah1,
  4. Bret L. Judson1,
  5. William E. Balch2

Article first published online: 30 JAN 2008

DOI: 10.1111/j.1600-0854.2008.00711.x

Issue

Traffic

Traffic

Volume 9, Issue 5, pages 786–797, May 2008

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How to Cite

Brown, W. J., Plutner, H., Drecktrah, D., Judson, B. L. and Balch, W. E. (2008), The Lysophospholipid Acyltransferase Antagonist CI-976 Inhibits a Late Step in COPII Vesicle Budding. Traffic, 9: 786–797. doi: 10.1111/j.1600-0854.2008.00711.x

Author Information

  1. 1

    Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA

  2. 2

    Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA

* *William J. Brown, wjb5@cornell.edu

Publication History

  1. Issue published online: 30 JAN 2008
  2. Article first published online: 30 JAN 2008
  3. Received 9 August 2007, revised and accepted for publication 23 January 2008, uncorrected manuscript published online 30 January 2008, published online 4 March 2008

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Keywords:

  • COPII vesicles;
  • ER exit sites;
  • lysophospholipid acyltransferase;
  • membrane curvature;
  • vesicle fission

The mechanism of coat protein (COP)II vesicle fission from the endoplasmic reticulum (ER) remains unclear. Lysophospholipid acyltransferases (LPATs) catalyze the conversion of various lysophospholipids to phospholipids, a process that can promote spontaneous changes in membrane curvature. Here, we show that 2,2-methyl-N-(2,4,6,-trimethoxyphenyl)dodecanamide (CI-976), a potent LPAT inhibitor, reversibly inhibited export from the ER in vivo and the formation of COPII vesicles in vitro. Moreover, CI-976 caused the rapid and reversible accumulation of cargo at ER exit sites (ERESs) containing the COPII coat components Sec23/24 and Sec13/31 and a marked enhancement of Sar1p-mediated tubule formation from ERESs, suggesting that CI-976 inhibits the fission of assembled COPII budding elements. These results identify a small molecule inhibitor of a very late step in COPII vesicle formation, consistent with fission inhibition, and demonstrate that this step is likely facilitated by an ER-associated LPAT.

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