β1 Syntrophin Supports Autophagy Initiation and Protects against Cerulein-Induced Acute Pancreatitis.

Abstract

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 β1 syntrophin, one of the least characterized members, we generated mouse models to eliminate β1 syntrophin specifically in the endocrine or exocrine pancreas. β1 syntrophin is dispensable for the morphology and function of insulin-producing β cells. However, mice with β1 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 β1 syntrophin is a critical regulator of actin cytoskeleton and autophagy in pancreatic acinar cells and is potently protective against cerulein-induced acute pancreatitis.

• Authors: Risheng Ye, Toshiharu Onodera, Pierre-Gilles Blanchard, Christine M Kusminski, Victoria Esser, Rolf A Brekken, Philipp E Scherer
• Journal: The American journal of pathology (Am J Pathol) Vol. 189 Issue 4 Pg. 813-825 (04 2019) ISSN: 1525-2191 [Electronic] United States
• PMID: 30653956 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cftr protein, mouse
• Dystrophin-Associated Proteins
• Protective Agents
• syntrophin
• Cystic Fibrosis Transmembrane Conductance Regulator
• Ceruletide

Topics

• Acinar Cells (drug effects, metabolism)
• Animals
• Autophagy
• Ceruletide (toxicity)
• Cystic Fibrosis Transmembrane Conductance Regulator (metabolism)
• Dystrophin-Associated Proteins (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Pancreas (drug effects, metabolism)
• Pancreatitis (chemically induced, metabolism, pathology, prevention & control)
• Protective Agents