Inhibition of a Golgi complex lysophospholipid acyltransferase induces membrane tubule formation and retrograde trafficking.
Recent studies have suggested that formation of Golgi membrane tubules involves the generation of membrane-associated lysophospholipids by a cytoplasmic Ca2+-independent phospholipase A2 (PLA2). Herein, we provide additional support for this idea by showing that inhibition of lysophospholipid reacylation by a novel Golgi-associated lysophosphatidylcholine acyltransferase (LPAT) induces the rapid tubulation of Golgi membranes, leading in their retrograde movement to the endoplasmic reticulum. Inhibition of the Golgi LPAT was achieved by 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide (CI-976), a previously characterized antagonist of acyl-CoA cholesterol acyltransferase. The effect of CI-976 was similar to that of brefeldin A, except that the coatomer subunit beta-COP remained on Golgi-derived membrane tubules. CI-976 also enhanced the cytosol-dependent formation of tubules from Golgi complexes in vitro and increased the levels of lysophosphatidylcholine in Golgi membranes. Moreover, preincubation of cells with PLA2 antagonists inhibited the ability of CI-976 to induce tubules. These results suggest that Golgi membrane tubule formation can result from increasing the content of lysophospholipids in membranes, either by stimulation of a PLA2 or by inhibition of an LPAT. These two opposing enzyme activities may help to coordinately regulate Golgi membrane shape and tubule formation.
Drecktrah
Daniel
D
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
Chambers
Kimberly
K
Racoosin
Esther L
EL
Cluett
Edward B
EB
Gucwa
Amy
A
Jackson
Brian
B
Brown
William J
WJ
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000215:Acylation; D000813:Anilides / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D006056:Golgi Apparatus / Q000201:enzymology*; D006367:HeLa Cells; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D013347:Subcellular Fractions
D000813:Anilides; D008244:Lysophosphatidylcholines; C069304:PD 128042; D020126:Brefeldin A; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D010741:Phospholipases A; D054467:Phospholipases A2