Phospholipase A2 antagonists inhibit constitutive retrograde membrane traffic to the endoplasmic reticulum.
Eukaryotic cells contain a variety of cytoplasmic Ca(2+)-dependent and Ca(2+)-independent phospholipase A2s (PLA2s; EC 2.3.1.2.3). However, the physiological roles for many of these ubiquitously-expressed enzymes is unclear or not known. Recently, pharmacological studies have suggested a role for Ca(2+)-independent PLA2 (iPLA2) enzymes in governing intracellular membrane trafficking events in general and regulating brefeldin A (BFA)-stimulated membrane tubulation and Golgi-to-endoplasmic reticulum (ER) retrograde membrane trafficking, in particular. Here, we extend these studies to show that membrane-permeant iPLA2 antagonists potently inhibit the normal, constitutive retrograde membrane trafficking from the trans-Golgi network (TGN), Golgi complex, and the ERGIC-53-positive ER-Golgi-intermediate compartment (ERGIC), which occurs in the absence of BFA. Taken together, these results suggest that iPLA2 enzymes play a general role in regulating, or directly mediating, multiple mammalian membrane trafficking events.
de Figueiredo
P
P
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Drecktrah
D
D
Polizotto
R S
RS
Cole
N B
NB
Lippincott-Schwartz
J
J
Brown
W J
WJ
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D020126:Brefeldin A / Q000494:pharmacology; D022181:COP-Coated Vesicles / Q000187:drug effects / Q000378:metabolism; D002999:Clone Cells; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015388:Organelles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D051381:Rats
D004791:Enzyme Inhibitors; C501458:Lman1 protein, rat; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D020126:Brefeldin A; D010741:Phospholipases A; D054467:Phospholipases A2