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cTAGE5 Interacts with Sec22b to Regulate Proinsulin Trafficking
Insulin is a peptide hormone, produced by pancreatic β cells, which is indispensable for proper maintenance of glucose homeostasis. Defects in insulin biogenesis may cause diabetes. Proinsulin, the precursor of insulin, is synthesized in the ER in pancreatic β cells and transported to the Golgi apparatus for proper processing and secretion into plasma. However, it was largely unknown the underlying mechanisms for proinsulin transport.
XU Zhiheng’s group from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, found that cTAGE5 interacts and is likely to coordinate with Sec22b to play an essential role in proinsulin trafficking from ER-to-Golgi.
They made use of Ins2-Cre to conditionally knockout the expression of cTAGE5 in pancreatic β cells, and found that ablation of cTAGE5 specifically in pancreatic β cells leaded to increased ER stress, reduced insulin biogenesis and severe glucose intolerance in mice, due to the defect in the transport of proinsulin from ER-to-Golgi.
In addition, they observed that cTAGE5 interacted with a V-SNARE protein Sec22b and the localization of Sec22b was disturbed in cTAGE5 cKO β cells. Furthermore, Sec22b and its interaction with cTAGE5 were essential for proinsulin processing.
Finally, they proposed a molecular model, in which cTAGE5 interacts with Sec22b, and they are likely to coordinate with each other in the release of COPII vesicle or the formation of the pre-Golgi intermediate compartment for proinsulin trafficking.
This work entitled “cTAGE5 Deletion in Pancreatic β Cells Impairs Proinsulin Trafficking and Insulin Biogenesis in Mice” was on-line published in the Journal of Cell Biology (JCB) on November 13th, 2017 (doi: 10.1083/jcb.201705027 ).
This work is supported by grants from National Natural Science Foundation of China and the Ministry of Science and Technology of China.
Scheme for the role of cTAGE5 and Sec22b in the ER-to-Golgi trafficking of proinsulin (Image by IGDB)
Dr. XU Zhiheng
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences