title: Characterization of a novel CI-976-sensitive lysophospholipid acyltransferase that is associated with the Golgi complex.
abstract: Recent studies have identified a novel lysophospholipid acyltransferase (LPAT) that is associated with the Golgi complex and that is sensitive to the previously characterized acyl-CoA cholesterol acyltransferase inhibitor, 2,2-methyl-N-(2,4,6-trimethoxyphenyl)dodecanamide (CI-976). Here we show that besides acting on exogenous lysophospholipid (LPL) substrates, the CI-976-sensitive LPAT is also capable of reacylating endogenous Golgi LPL substrates, preferentially lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). Moreover, using exogenous substrates, we find that the CI-976-sensitive LPAT is capable of using a variety of fatty acyl-CoA donors ranging in chain length from 10 to 20 carbons. Additional characterization demonstrates that the CI-976-sensitive LPAT is ubiquitously expressed in rat tissues, is tightly associated with Golgi membranes, and has a pH optimum between pH 7.0 and 8.0. These studies further define a unique LPC/LPE-specific LPAT from Golgi membranes that likely has a novel function in membrane trafficking.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Chambers
authors.forename: William J
authors.initials: WJ
authors.lastname: Brown
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000096:biosynthesis* / Q000737:chemistry*; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D002244:Carbon / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000813:Anilides; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; C008301:lysophosphatidylethanolamine; C069304:PD 128042; D002244:Carbon; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C481524:CI-976-sensitive lysophospholipid acyltransferase