TY - JOUR
T1 - Changes in Rab3D expression and distribution in the acini of Sjögren's syndrome patients are associated with loss of cell polarity and secretory dysfunction
AU - Bahamondes, Verõnica
AU - Albornoz, Amelina
AU - Aguilera, Sergio
AU - Alliende, Cecilia
AU - Molina, Claudio
AU - Castro, Isabel
AU - Urzúa, Ulises
AU - Quest, Andrew F.G.
AU - Barrera, María José
AU - González, Sergio
AU - Sánchez, Marianela
AU - Härtel, Steffen
AU - Hermoso, Marcela
AU - Leyton, Cecilia
AU - González, María Julieta
PY - 2011/10
Y1 - 2011/10
N2 - 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. Conclusion 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.
AB - 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. Conclusion 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.
UR - http://www.scopus.com/inward/record.url?scp=80053521118&partnerID=8YFLogxK
U2 - 10.1002/art.30500
DO - 10.1002/art.30500
M3 - Article
C2 - 21702009
AN - SCOPUS:80053521118
SN - 0004-3591
VL - 63
SP - 3126
EP - 3135
JO - Arthritis and Rheumatism
JF - Arthritis and Rheumatism
IS - 10
ER -