A role for phospholipase A2 activity in membrane tubule formation and TGN trafficking.
We have investigated the role of phospholipase A(2) (PLA(2) ) enzymes in generating membrane tubules at the trans-Golgi network (TGN). Constitutive TGN membrane tubules and those induced by over-expressing kinase dead protein kinase D were inhibited by the PLA(2) inhibitors ONO-RS-082 (ONO) and bromoenol lactone. These antagonists also inhibited secretory delivery of both soluble and transmembrane cargoes. Finally, use of the reversible antagonist ONO and time-lapse imaging revealed for the first time that PLA(2) antagonists inhibit the initiation of membrane tubule formation at the TGN. Thus, PLA(2) enzymes appear to have an important role in the earliest steps of membrane tubule formation at the TGN, which are utilized for membrane trafficking.
Schmidt
John A
JA
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Kalkofen
Danielle N
DN
Donovan
Kirk W
KW
Brown
William J
WJ
D062365:Aminobenzoates / Q000494:pharmacology; D002460:Cell Line; D002723:Chlorobenzoates; D002934:Cinnamates / Q000494:pharmacology; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000502:physiology*; D054522:Group VI Phospholipases A2 / Q000235:genetics / Q000502:physiology; D006801:Humans; D009281:Naphthalenes / Q000494:pharmacology; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D011753:Pyrones / Q000494:pharmacology; D062367:ortho-Aminobenzoates; D021601:trans-Golgi Network / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D062365:Aminobenzoates; D002723:Chlorobenzoates; D002934:Cinnamates; D009281:Naphthalenes; D011506:Proteins; D011753:Pyrones; D062367:ortho-Aminobenzoates; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; C060048:2-(4-amylcinnamoyl)amino-4-chlorobenzoic acid; D054513:Group IV Phospholipases A2; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human