title: The orthologue of Sjögren's syndrome nuclear autoantigen 1 (SSNA1) in Trypanosoma brucei is an immunogenic self-assembling molecule.
abstract: Primary Sjögren's Syndrome (PSS) is a highly prevalent autoimmune disease, typically manifesting as lymphocytic infiltration of the exocrine glands leading to chronically impaired lacrimal and salivary secretion. Sjögren's Syndrome nuclear autoantigen 1 (SSNA1 or NA14) is a major specific target for autoantibodies in PSS but the precise function and clinical relevance of this protein are largely unknown. Orthologues of the gene are absent from many of the commonly used model organisms but are present in Chlamyodomonas reinhardtii (in which it has been termed DIP13) and most protozoa. We report the functional characterisation of the orthologue of SSNA1 in the kinetoplastid parasite, Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins which are predicted to be remote homologues of the actin-binding protein tropomyosin. We use comparative proteomic methods to identify potential interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to self-assemble into fibril-like structures both in vitro and in vivo, a property which may contribute to its immunogenicity. Endogenous TbDIP13 partially co-localises with acetylated α-tubulin in the insect procyclic stage of the parasite. However, deletion of the DIP13 gene in cultured bloodstream and procyclic stages of T. brucei has little effect on parasite growth or morphology, indicating either a degree of functional redundancy or a function in an alternative stage of the parasite life cycle.
authors.affiliation: Centre for Immunology and Infection, Department of Biology, University of York, Heslington, York, United Kingdom. helen.price@york.ac.uk
authors.forename: Helen P
authors.initials: HP
authors.lastname: Price
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hodgkinson
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Curwen
authors.forename: Lorna M
authors.initials: LM
authors.lastname: MacLean
authors.forename: James A
authors.initials: JA
authors.lastname: Brannigan
authors.forename: Mark
authors.initials: M
authors.lastname: Carrington
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Smith
authors.forename: David A
authors.initials: DA
authors.lastname: Ashford
authors.forename: Meg
authors.initials: M
authors.lastname: Stark
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Smith
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry*; D002470:Cell Survival; D017353:Gene Deletion; D017125:Genes, Protozoan / Q000235:genetics; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry*; D010271:Parasites / Q000276:immunology; D021381:Protein Transport; D040901:Proteomics; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid; D012859:Sjogren's Syndrome / Q000276:immunology*; D013347:Subcellular Fractions / Q000378:metabolism; D014335:Tropomyosin / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000166:cytology / Q000235:genetics / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000097:blood / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D001324:Autoantigens; C110204:NA14 nuclear autoantigen; D009687:Nuclear Proteins; D015800:Protozoan Proteins; D014335:Tropomyosin