Amyloid beta regulates ER exit sites formation through O-GlcNAcylation triggered by disrupted calcium homeostasis.

摘要: Background information Aberrant production of amyloid beta (Aβ) causes disruption intracellular calcium homeostasis, a crucial factor in the pathogenesis Alzheimer's disease. Calcium is required for fusion and trafficking vesicles. Previously, we demonstrated that Sec31A, main component coat protein complex II (COPII) vesicles at ER exit sites (ERES), modulated by O-GlcNAcylation. O-GlcNAcylation, unique dynamic glycosylation process, modulates formation COPII Results In this study, observed disrupted levels affected ERES through calcium-triggered O-GlcNAcylation Sec31A. Additionally, found Aβ impaired Aβ-disturbed homeostasis Sec31A neuronal cells. Furthermore, identified ribbon-like structure Golgi. Golgi fragmentation was rescued up-regulation O-GlcNAcylaion using Thiamet G (ThiG), an O-GlcNAcase inhibitor. reassembly stacking proteins having function showed attenuation following treatment. Conclusions This study targeting to altered triggered homeostasis. Significance The findings suggested protection or Sec31 may offer promising novel avenue development AD therapeutics.