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The Lysophospholipid Acyltransferase Antagonist CI‐976 Inhibits a Late Step in COPII Vesicle Budding
Author(s) -
Brown William J.,
Plutner Helen,
Drecktrah Daniel,
Judson Bret L.,
Balch William E.
Publication year - 2008
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2008.00711.x
Subject(s) - copii , copi , endoplasmic reticulum , vesicle , microbiology and biotechnology , biology , vesicular transport proteins , golgi apparatus , budding , membrane curvature , biochemistry , secretory pathway , membrane , vacuole , cytoplasm , vacuolar protein sorting
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.