Impaired GATE16-mediated exocytosis in exocrine tissues causes Sjögren’s syndrome-like exocrinopathy

Akiko Suzuki, Chihiro Iwaya, Kenichi Ogata, Hiroki Yoshioka, Junbo Shim, Isei Tanida, Masaaki Komatsu, Norihiro Tada, Junichi Iwata

研究成果: ジャーナルへの寄稿学術誌査読

抄録

Sjögren’s syndrome (SjS) is a chronic autoimmune disease characterized by immune cell infiltration of the exocrine glands, mainly the salivary and lacrimal glands. Despite recent advances in the clinical and mechanistic characterization of the disease, its etiology remains largely unknown. Here, we report that mice with a deficiency for either Atg7 or Atg3, which are enzymes involved in the ubiquitin modification pathway, in the salivary glands exhibit a SjS-like phenotype, characterized by immune cell infiltration with autoantibody detection, acinar cell death, and dry mouth. Prior to the onset of the SjS-like phenotype in these null mice, we detected an accumulation of secretory vesicles in the acinar cells of the salivary glands and found that GATE16, an uncharacterized autophagy-related molecule activated by ATG7 (E1-like enzyme) and ATG3 (E2-like enzyme), was highly expressed in these cells. Notably, GATE16 was activated by isoproterenol, an exocytosis inducer, and localized on the secretory vesicles in the acinar cells of the salivary glands. Failure to activate GATE16 was correlated with exocytosis defects in the acinar cells of the salivary glands in Atg7 and Atg3 cKO mice. Taken together, our results show that GATE16 activation regulated by the autophagic machinery is crucial for exocytosis and that defects in this pathway cause SjS.

本文言語英語
論文番号307
ジャーナルCellular and Molecular Life Sciences
79
6
DOI
出版ステータス出版済み - 6月 2022
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 分子生物学
  • 薬理学
  • 細胞および分子神経科学
  • 細胞生物学

フィンガープリント

「Impaired GATE16-mediated exocytosis in exocrine tissues causes Sjögren’s syndrome-like exocrinopathy」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル