Abstract
Sjögren’s disease is a chronic autoimmune disease characterized by symptoms of oral and ocular dryness and extraglandular manifestations. Mouth dryness is not only due to reduced saliva volume, but also to alterations in the quality of salivary mucins in patients with Sjögren’s disease. Mucins play a leading role in mucosa hydration and protection, where sulfated and sialylated oligosaccharides retain water molecules at the epithelial surface. The correct localization of glycosyltransferases and sulfotransferases within the Golgi apparatus determines adequate O-glycosylation and sulfation of mucins, which depends on specific golgins that tether enzyme-bearing vesicles. Here, we show that a golgin called Giantin was mislocalized in salivary glands from patients with Sjögren’s disease and formed protein complexes with Gal3-O-sulfotransferases (Gal3STs), which changed their localization in Giantin-knockout and -knockdown cells. Our results suggest that Giantin could tether Gal3ST-bearing vesicles and that its altered localization could affect Gal3ST activity, explaining the decreased sulfation of MUC5B observed in salivary glands from patients with Sjögren’s disease.
Authors
Matilde Nuñez, Patricia Carvajal, Sergio Aguilera, María-José Barrera, Soledad Matus, Alicia Couto, Malena Landoni, Gaelle Boncompain, Sergio González, Claudio Molina, Karina Pino, Sebastián Indo, Lourdes Figueroa, María-Julieta González, Isabel Castro
Figure 10
Decreased abundance of MUC5B-associated oligosaccharides in LSGs from patients with SjD.
