Phospholipase A(2) antagonists inhibit constitutive retrograde membrane traffic to the endoplasmic reticulum

Eukaryotic cells contain a variety of cytoplasmic Ca2+-dependent and Ca2+-i ndependent phospholipase A(2)s (PLA(2)s; EC 2.3.1.2.3). However, the physio logical roles for many of these ubiquitously-expressed enzymes is unclear o r not known. Recently, pharmacological studies have suggested a role for Ca 2+-independent PLA(2) (iPLA(2)) enzymes in governing intracellular membrane trafficking events in general and regulating brefeldin A (BFA)-stimulated membrane tubulation and Golgi-to-endoplasmic reticulum (ER) retrograde memb rane trafficking, in particular. Here, we extend these studies to show that membrane-permeant iPLA(2) antagonists potently inhibit the normal, constit utive retrograde membrane trafficking from the trans-Golgi network (TGN), G olgi complex, and the ERGIC-53-positive ER-Golgi-intermediate compartment ( ERGIC), which occurs in the absence of BFA. Taken together, these results s uggest that iPLA(2) enzymes play a general role in regulating, or directly mediating, multiple mammalian membrane trafficking events.