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, alpha1 and alpha2, and a third subunit, the dynein regulator lissencephaly 1 (LIS1), mediates the structure and function of the Golgi complex. Both alpha1 and alpha2 partially localize on Golgi membranes, and purified catalytically active, but not inactive alpha1 and alpha2 induce Golgi membrane tubule formation in a reconstitution system. Overexpression of wild-type or mutant alpha1 or alpha2 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 alpha1 and alpha2 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.
Bechler
Marie E
ME
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Doody
Anne M
AM
Racoosin
Esther
E
Lin
Lin
L
Lee
Kelvin H
KH
Brown
William J
WJ
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000201:enzymology* / Q000648:ultrastructure*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008869:Microtubule-Associated Proteins; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; C516550:Pafah1b1 protein, rat; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human