The lysophospholipid acyltransferase antagonist CI-976 inhibits a late step in COPII vesicle budding

William J. Brown, Helen Plutner, Daniel Drecktrah, Bret L. Judson, William E. Balch

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)786-797
Number of pages12
JournalTraffic
Volume9
Issue number5
DOIs
StatePublished - May 2008

Keywords

  • COPII vesicles
  • ER exit sites
  • Lysophospholipid acyltransferase
  • Membrane curvature
  • Vesicle fission

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