de Figueiredo P, Drecktrah D, Polizotto R S, Cole N B, Lippincott-Schwartz J, Brown W J
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Traffic. 2000 Jun;1(6):504-11. doi: 10.1034/j.1600-0854.2000.010608.x.
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.
真核细胞含有多种细胞质钙离子依赖性和非钙离子依赖性磷脂酶A2（PLA2s；EC 2.3.1.2.3）。然而，这些广泛表达的酶中许多的生理作用尚不清楚或未知。最近，药理学研究表明，非钙离子依赖性磷脂酶A2（iPLA2）酶总体上在控制细胞内膜运输事件中起作用，特别是在调节布雷菲德菌素A（BFA）刺激的膜微管形成以及高尔基体到内质网（ER）的逆行膜运输中起作用。在此，我们扩展这些研究以表明，膜渗透性iPLA2拮抗剂能有效抑制在不存在BFA的情况下从反式高尔基体网络（TGN）、高尔基体复合体和ERGIC-53阳性的内质网-高尔基体中间区室（ERGIC）发生的正常组成型逆行膜运输。综上所述，这些结果表明iPLA2酶在调节或直接介导多种哺乳动物膜运输事件中起普遍作用。
