Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas

摘要: Intracellular galectins are carbohydrate-binding proteins capable of sensing and repairing damaged lysosomes. As in the physiological conditions glycosylated moieties mostly lysosomal lumen but not cytosol, it is unclear whether reside lysosomes, bind to proteins, regulate lysosome functions. Here, we show gut epithelial cells, galectin-9 enriched lysosomes predominantly binds lysosome-associated membrane protein 2 (Lamp2) a Asn(N)-glycan dependent manner. At steady state, binding Asn175 Lamp2 essential for functionality autophagy. Loss N-glycan-binding capability causes its complete depletion from defective autophagy, leading increased endoplasmic reticulum (ER) stress preferentially autophagy-active Paneth cells acinar cells. Unresolved ER consequently cell degeneration or apoptosis that associates with colitis pancreatic disorders mice. Therefore, maintain homeostatic function prevent organ pathogenesis.