title: Systematic proteomics of the VCP-UBXD adaptor network identifies a role for UBXN10 in regulating ciliogenesis.
abstract: The AAA-ATPase VCP (also known as p97 or CDC48) uses ATP hydrolysis to 'segregate' ubiquitylated proteins from their binding partners. VCP acts through UBX-domain-containing adaptors that provide target specificity, but the targets and functions of UBXD proteins remain poorly understood. Through systematic proteomic analysis of UBXD proteins in human cells, we reveal a network of over 195 interacting proteins, implicating VCP in diverse cellular pathways. We have explored one such complex between an unstudied adaptor UBXN10 and the intraflagellar transport B (IFT-B) complex, which regulates anterograde transport into cilia. UBXN10 localizes to cilia in a VCP-dependent manner and both VCP and UBXN10 are required for ciliogenesis. Pharmacological inhibition of VCP destabilized the IFT-B complex and increased trafficking rates. Depletion of UBXN10 in zebrafish embryos causes defects in left-right asymmetry, which depends on functional cilia. This study provides a resource for exploring the landscape of UBXD proteins in biology and identifies an unexpected requirement for VCP-UBXN10 in ciliogenesis.
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Malavika
authors.initials: M
authors.lastname: Raman
authors.affiliation: Department of Systems Biology, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.|Renal Division, Brigham and Women's Hospital, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Sergeev
authors.affiliation: Department of Medicine, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.|Department of Health Science and Technology, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Maija
authors.initials: M
authors.lastname: Garnaas
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Lydeard
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Huttlin
authors.affiliation: Department of Medicine, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.|Department of Health Science and Technology, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Goessling
authors.affiliation: Department of Systems Biology, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.|Renal Division, Brigham and Women's Hospital, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.|Harvard-MIT, Division of Health Sciences and Technology, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
authors.forename: Jagesh V
authors.initials: JV
authors.lastname: Shah
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: J Wade
authors.initials: JW
authors.lastname: Harper
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism* / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D018374:LLC-PK1 Cells; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009024:Morphogenesis / Q000502:physiology; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D034622:RNA Interference; D013552:Swine; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000074405:Valosin Containing Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C490080:IFT74 protein, human; C098623:IFT88 protein, human; D025521:Tumor Suppressor Proteins; C000604314:UBXN10 protein, human; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein