title: Changes in Rab3D expression and distribution in the acini of Sjögren's syndrome patients are associated with loss of cell polarity and secretory dysfunction.
abstract: OBJECTIVE
  Oral and ocular dryness are frequent and serious symptoms of Sjögren's syndrome (SS) that reflect problems in secretion due to glandular dysfunction. Exocytosis, an important process in the secretory pathway, requires the participation of Rab family GTPases. This study was undertaken to analyze the expression and localization of Rab3D and Rab8A and to examine their correlation with acinar cell polarity and glandular secretory function.
  
  
  METHODS
  Nineteen patients with SS and 17 controls were evaluated. Levels of Rab3D and Rab8A messenger RNA (mRNA) and protein were determined by real-time polymerase chain reaction and Western blotting. Subcellular localization of proteins was determined by indirect immunofluorescence analysis.
  
  
  RESULTS
  In patients with SS, total Rab3D protein levels decreased significantly, while mRNA levels remained unchanged. For Rab8A, no changes in either mRNA or protein levels were detected. In serous acini of labial salivary glands from patients with SS, the following 4 patterns of Rab3D staining were distinguishable: severely decreased, distribution throughout the cytoplasm, distribution throughout the cytoplasm combined with loss of nuclear polarity, and normal apical localization. Basal localization of Rab8A was not modified. Rab3D changes were accompanied by apicobasolateral redistribution of ezrin, loss of nuclear polarity, thicker Golgi stacks, and mucin 7 accumulation in the cytoplasm. Finally, low Rab3D protein levels correlated with alterations in scintigraphy measurements.
  
  
  CONCLUSIONS
  Our findings indicate that Rab3D regulates the exocytosis of many components critical for the maintenance of oral physiology. Hence, the changes observed in Rab3D expression and distribution are likely to contribute to the decrease in or loss of saliva components (i.e., mucins), which may explain the variety of oral and ocular symptoms associated with SS.
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, University of Chile, Santiago, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: Bahamondes
authors.forename: Amelina
authors.initials: A
authors.lastname: Albornoz
authors.forename: Sergio
authors.initials: S
authors.lastname: Aguilera
authors.forename: Cecilia
authors.initials: C
authors.lastname: Alliende
authors.forename: Claudio
authors.initials: C
authors.lastname: Molina
authors.forename: Isabel
authors.initials: I
authors.lastname: Castro
authors.forename: Ulises
authors.initials: U
authors.lastname: Urzúa
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
authors.forename: María-José
authors.initials: MJ
authors.lastname: Barrera
authors.forename: Sergio
authors.initials: S
authors.lastname: González
authors.forename: Marianela
authors.initials: M
authors.lastname: Sánchez
authors.forename: Steffen
authors.initials: S
authors.lastname: Härtel
authors.forename: Marcela
authors.initials: M
authors.lastname: Hermoso
authors.forename: Cecilia
authors.initials: C
authors.lastname: Leyton
authors.forename: María-Julieta
authors.initials: MJ
authors.lastname: González
mesh_terms: D000328:Adult; D016764:Cell Polarity / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012469:Salivary Glands / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C492134:RAB3D protein, human; C082377:RAB8A protein, human; D020691:rab GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins