The phospholipase complex PAFAH Ib regulates the functional organization of the Golgi complex

Abstract

We report that platelet-activating factor acetylhydrolase (PAFAH) Ib, comprised of two phospholipase A2 (PLA2) subunits, α1 and α2, and a third subunit, the dynein regulator lissencephaly 1 (LIS1), mediates the structure and function of the Golgi complex. Both α1 and α2 partially localize on Golgi membranes, and purified catalytically active, but not inactive α1 and α2 induce Golgi membrane tubule formation in a reconstitution system. Overexpression of wild-type or mutant α1 or α2 revealed that both PLA2 activity and LIS1 are important for maintaining Golgi structure. Knockdown of PAFAH Ib subunits fragments the Golgi complex, inhibits tubule-mediated reassembly of intact Golgi ribbons, and slows secretion of cargo. Our results demonstrate a cooperative interplay between the PLA2 activity of α1 and α2 with LIS1 to facilitate the functional organization of the Golgi complex, thereby suggesting a model that links phospholipid remodeling and membrane tubulation to dynein-dependent transport.