beta 1 Syntrophin Supports Autophagy Initiation and Protects against Cerulein-Induced Acute Pancreatitis

摘要

Syntrophins are a family of proteins forming membrane-anchored scaffolds and serving as adaptors for various transmembrane and intracellular signaling molecules. To understand the physiological roles of beta 1 syntrophin, one of the least characterized members, we generated mouse models to eliminate beta 1 syntrophin specifically in the endocrine or exocrine pancreas. beta 1 syntrophin is dispensable for the morphology and function of insulin-producing cells. However, mice with beta 1 syntrophin deletion in exocrine acinar cells exhibit increased severity of ceruLein-induced acute pancreatitis. Reduced expression of cystic fibrosis transmembrane conductance regulator and dilation of acinar lumen are potential predisposition factors. During the disease progression, a relative lack of autophagy is associated with deficiencies in both actin assembly and endoplasmic reticulum nucleation. Our findings reveal, for the first time, that beta 1 syntrophin is a critical regulator of actin cytoskeleton and autophagy in pancreatic acinar cells and is potently protective against cerulein-induced acute pancreatitis.