Phospholipase A2 antagonists inhibit constitutive retrograde membrane traffic to the endoplasmic reticulum

Eukaryotic cells contain a variety of cytoplasmic Ca2+-dependent and Ca2+-independent phospholipase A(2)s (PLA(2)s; 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 Ca2+-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 membrane trafficking, in particular. Here, we extend these studies to show that membrane-permeant iPLA(2) 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 iPLA(2) enzymes play a general role in regulating, or directly mediating, multiple mammalian membrane trafficking events.