| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Formation of disulfide bonds is a crucial step in the folding of a huge number of secretory proteins. The ER of mammalian cells houses twenty PDI family members, which are supposed to catalyze disulfide bond formation in secretory proteins. PDIp is a PDI family member predominantly expressed in the pancreas. Here, we show that PDIp interacts directly with a number of digestive enzymes in vivo and assists in the folding of one of these enzymes, leading to our proposal that PDIp is a PDI family member dedicated to the folding of pancreatic digestive enzymes. Furthermore, we show that IRE1α, an ER stress sensor, plays a crucial role in the production of insulin by upregulating the biosynthesis of some PDI family members. These findings provide new insights into the disulfide bond formation system of mammalian cells.
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