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

We report that platelet-activating factor acetylhydrolase (PAFAH) Ib, comprised of two phospholipase A(2) (PLA(2)) subunits, alpha 1 and alpha 2, and a third subunit, the dynein regulator lissencephaly 1 (LIS1), mediates the structure and function of the Golgi complex. Both alpha 1 and alpha 2 partially localize on Golgi membranes, and purified catalytically active, but not inactive alpha 1 and alpha 2 induce Golgi membrane tubule formation in a reconstitution system. Overexpression of wild-type or mutant alpha 1 or alpha 2 revealed that both PLA(2) 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 PLA(2) activity of alpha 1 and alpha 2 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.