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题名: Insulin-regulated Aminopeptidase Is a Key Regulator of GLUT4 Trafficking by Controlling Sorting from Endosomes to Specialized Insulin-regulated Vesicles
作者: Ingrid Jordens ; Dorothee Molle ; null(熊文勇) ; Susanna R. Keller ; Timothy McGraw
刊名: Molecular Biology of the Cell
英文摘要: Insulin stimulates glucose uptake by regulating translocation of the GLUT4 glucose transporter from intracellular compartments to the plasma membrane. In the absence of insulin GLUT4 is actively sequestered away from the general endosomes into GLUT4-specialized compartments, thereby controlling the amount of GLUT4 at the plasma membrane. Here, we investigated the role of the aminopeptidase IRAP in GLUT4 trafficking. In unstimulated IRAP knockdown adipocytes, plasma membrane GLUT4 levels are elevated because of increased exocytosis, demonstrating an essential role of IRAP in GLUT4 retention. Current evidence supports the model that AS160 RabGAP, which is required for basal GLUT4 retention, is recruited to GLUT4 compartments via an interaction with IRAP. However, here we show that AS160 recruitment to GLUT4 compartments and AS160 regulation of GLUT4 trafficking were unaffected by IRAP knockdown. These results demonstrate that AS160 is recruited to membranes by an IRAP-independent mechanism. Consistent with a role independent of AS160, we showed that IRAP functions in GLUT4 sorting from endosomes to GLUT4-specialized compartments. This is revealed by the relocalization of GLUT4 to endosomes in IRAP knockdown cells. Although IRAP knockdown has profound effects on GLUT4 traffic, GLUT4 knockdown does not affect IRAP trafficking, demonstrating that IRAP traffics independent of GLUT4. In sum, we show that IRAP is both cargo and a key regulator of the insulin-regulated pathway.
出版日期: 2010
卷号: 21, 期号:12, 页码:2034-2044
收录类别: SCI
内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/17697
Appears in Collections:植物化学与西部植物资源持续利用国家重点实验室_期刊论文

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文件名: 5.Insulin-regulated Aminopeptidase Is a Key Regulator of GLUT4 Trafficking by Controlling Sorting from Endosomes to Specialized Insulin-regulated Vesicles.2010.pdf
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