title: Aberrant localization of fusion receptors involved in regulated exocytosis in salivary glands of Sjögren's syndrome patients is linked to ectopic mucin secretion.
abstract: Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that mainly affects tear and salivary glands, whereby SS-patients frequently complain of eye and mouth dryness. Salivary acinar cells of SS-patients display alterations in their cell polarity; which may affect the correct localization and function of proteins involved in regulated exocytosis. Here we determined whether the expression and localization of SNARE proteins (membrane fusion receptors) involved in regulated secretion, such as VAMP8, syntaxin 3 (STX3), STX4 and SNAP-23 were altered in salivary glands (SG) from SS-patients. Additionally, we investigated SNARE proteins function, by evaluating their ability to form SNARE complexes under basal conditions. In SG from SS-patients and control subjects mRNA and proteins levels of SNARE complex components were determined by real-time PCR and Western blotting, respectively. SNARE protein distribution and mucin exocytosis were determined by indirect immunofluorescence. In SS-patients, the expression levels of mRNA and protein for VAMP8, STX4 and STX3 were altered. STX4, STX3, SNAP-23 and VAMP8 relocated from the apical to the basal region of acinar cells. Increased formation of SNARE complexes in a manner independent of external stimuli for secretion was detected. Mucins were detected in the extracellular matrix (ECM). Presence of mucins in the ECM, together with the observed alterations in SNARE protein localization is indicative of ectopic exocytosis. In the context of SS, such aberrantly localized mucins are likely to favor a pro-inflammatory response, which may represent an important initial step in the pathogenesis of this disease.
authors.affiliation: Faculty of Medicine, Institute of Biomedical Sciences (ICBM), University of Chile, Postal Code 8389100, Santiago, Chile.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Barrera
authors.forename: Marianela
authors.initials: M
authors.lastname: Sánchez
authors.forename: Sergio
authors.initials: S
authors.lastname: Aguilera
authors.forename: Cecilia
authors.initials: C
authors.lastname: Alliende
authors.forename: Verónica
authors.initials: V
authors.lastname: Bahamondes
authors.forename: Claudio
authors.initials: C
authors.lastname: Molina
authors.forename: Andrew F G
authors.initials: AF
authors.lastname: Quest
authors.forename: Ulises
authors.initials: U
authors.lastname: Urzúa
authors.forename: Isabel
authors.initials: I
authors.lastname: Castro
authors.forename: Sergio
authors.initials: S
authors.lastname: González
authors.forename: Hsiao Hsin
authors.initials: HH
authors.lastname: Sung
authors.forename: Amelina
authors.initials: A
authors.lastname: Albornoz
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: D061354:Acinar Cells / Q000378:metabolism; D000328:Adult; D015551:Autoimmunity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000378:metabolism*
chemical_list: D009077:Mucins; D050600:SNARE Proteins