Giantin mediates Golgi localization of Gal3-O-sulfotransferases and affects salivary mucin sulfation in patients with Sjögren’s disease

Abstract

Sjögren’s disease is a chronic autoimmune disease characterized by symptoms of oral and oculardryness and extraglandular manifestations. Mouth dryness is not only due to reduced salivavolume, 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 sialylatedoligosaccharides retain water molecules at the epithelial surface. The correct localization ofglycosyltransferases and sulfotransferases within the Golgi apparatus determines adequateO-glycosylation and sulfation of mucins, which depends on specific golgins that tether enzymebearing vesicles. Here, we show that a golgin called Giantin was mislocalized in salivary glandsfrom 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 resultssuggest that Giantin could tether Gal3ST-bearing vesicles and that its altered localization couldaffect Gal3ST activity, explaining the decreased sulfation of MUC5B observed in salivary glandsfrom patients with Sjögren’s disease.