biostudies-literatureFan JChinese Academy of SciencesNational Science Foundation of China4153-4164https://www.ebi.ac.uk/biostudies/studies/S-EPMC5716288biostudies-literatureUnknown216(12)Proinsulin is synthesized in the endoplasmic reticulum (ER) in pancreatic β cells and transported to the Golgi apparatus for proper processing and secretion into plasma. Defects in insulin biogenesis may cause diabetes. However, the underlying mechanisms for proinsulin transport are still not fully understood. We show that β cell-specific deletion of <i>cTAGE5</i>, also known as <i>Mea6</i>, leads to increased ER stress, reduced insulin biogenesis in the pancreas, and severe glucose intolerance in mice. We reveal that cTAGE5/MEA6 interacts with vesicle membrane soluble <i>N</i>-ethyl-maleimide sensitive factor attachment protein receptor Sec22b. Sec22b and its interaction with cTAGE5/MEA6 are essential for proinsulin processing. cTAGE5/MEA6 may coordinate with Sec22b to control the releaseThe Journal of cell biology<i>cTAGE5</i> deletion in pancreatic β cells impairs proinsulin trafficking and insulin biogenesis in mice.PMC5716288QYZDJ-SSW-SMC007/GJHZ182731771569/31471132/31430037/31571038/31730108Zhang FShi LYu MLiu LFan JZhang HWang YGao FXu Zfalse<i>cTAGE5</i> deletion in pancreatic β cells impairs proinsulin trafficking and insulin biogenesis in mice.Proinsulin is synthesized in the endoplasmic reticulum (ER) in pancreatic β cells and transported to the Golgi apparatus for proper processing and secretion into plasma. Defects in insulin biogenesis may cause diabetes. However, the underlying mechanisms for proinsulin transport are still not fully understood. We show that β cell-specific deletion of <i>cTAGE5</i>, also known as <i>Mea6</i>, leads to increased ER stress, reduced insulin biogenesis in the pancreas, and severe glucose intolerance in mice. We reveal that cTAGE5/MEA6 interacts with vesicle membrane soluble <i>N</i>-ethyl-maleimide sensitive factor attachment protein receptor Sec22b. Sec22b and its interaction with cTAGE5/MEA6 are essential for proinsulin processing. cTAGE5/MEA6 may coordinate with Sec22b to control the release2017-01-01T00:00:00Z2017 Dec2026-05-05T21:11:33.136Z2019-06-06T18:33:12ZS-EPMC57162882913348310.1083/jcb.201705027