Intracellular phospholipase A_1γ(iPLA_1γ) is a novel factor involved in coat protein complex I-and Rab6-independent retrograde transport between the endoplasmic reticulum and the golgi complex

The mammalian intracellular phospholipase A₁ (iPLA₁) family consists of three members, iPLA₁α/PA-PLA₁, iPLA₁β/p125, and iPLA₁γ/KIAA0725p. Although iPLA₁β has been implicated in organization of the ER-Golgi compartments, little is known about the physiological role of its closest paralog, iPLA₁γ. Here we show that iPLA₁γ mediates a specific retrograde membrane transport pathway between the endoplasmic reticulum (ER) and the Golgi complex. iPLA₁γ appeared to be localized to the cytosol, the cis-Golgi, and the ER-Golgi intermediate compartment (ERGIC). Time-lapse microscopy revealed that a population of GFP-iPLA₁γ was associated with transport carriers moving out from the Golgi complex. Knockdown of iPLA₁γ expression by RNAi did not affect the anterograde transport of VSVGts045 but dramatically delayed two types of Golgi-to-ER retrograde membrane transport; that is, transfer of the Golgi membrane into the ER in the presence of brefeldin A and delivery of cholera toxin B subunit from the Golgi complex to the ER. Notably, knockdown of iPLA₁γ did not impair COPI- and Rab6-dependent retrograde transports represented by ERGIC-53 recycling and ER delivery of Shiga toxin, respectively. Thus, iPLA₁γ is a novel membrane transport factor that contributes to a specific Golgi-to-ER retrograde pathway distinct from presently characterized COPI- and Rab6-dependent pathways.