title: Distinct sets of Rab6 effectors contribute to ZW10--and COG-dependent Golgi homeostasis.
abstract: The organization of the Golgi apparatus is determined in part by the interaction of Rab proteins and their diverse array of effectors. Here, we used multiple approaches to identify and characterize a small subset of effectors that mimicked the effects of Rab6 on Golgi ribbon organization. In a visual-based, candidate protein screen, we found that the individual depletion of any of three Rab6 effectors, myosin IIA (MyoIIA), Kif20A and Bicaudal D (BicD), was sufficient to suppress Golgi ribbon fragmentation/dispersal coupled to retrograde tether proteins in a manner paralleling Rab6. MyoIIA and Kif20A depletions were pathway selective and suppressed ZW10-dependent Golgi ribbon fragmentation/dispersal only whereas BicD depletion, like Rab6, suppressed both ZW10- and COG-dependent Golgi ribbon fragmentation. The MyoIIA effects could be produced in short-term assays by the reversible myosin inhibitor, blebbistatin. At the electron microscope level, the effects of BicD-depletion mimicked many of those of Rab6-depletion: longer and more continuous Golgi cisternae and a pronounced accumulation of coated vesicles. Functionally, BicD-depleted cells were inhibited in transport of newly synthesized VSV-G protein to the cell surface. In summary, our results indicate small, partially overlapping subsets of Rab6 effectors are differentially important to two tether-dependent pathways essential to Golgi organization and function.
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
authors.forename: Waqar
authors.initials: W
authors.lastname: Majeed
authors.forename: Shijie
authors.initials: S
authors.lastname: Liu
authors.forename: Brian
authors.initials: B
authors.lastname: Storrie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D018699:Coated Vesicles / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C109571:BICD1 protein, human; C561542:BICD2 protein, human; C498528:COG3 protein, human; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; C028391:G protein, vesicular stomatitis virus; C410089:KIF20A protein, human; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; C094135:Rab6 protein; D014759:Viral Envelope Proteins; C488261:ZW10 protein, human; D024507:Nonmuscle Myosin Type IIA; D016547:Kinesins; D020691:rab GTP-Binding Proteins
keywords: COG; Golgi apparatus; Golgi homeostasis; Rab6; Rab6 effectors; ZW10