Insulin-regulated aminopeptidase is a key regulator of GLUT4 trafficking by controlling the sorting of GLUT4 from endosomes to specialized insulin-regulated vesicles.
Insulin-regulated aminopeptidase is a key regulator of GLUT4 trafficking by controlling the sorting of GLUT4 from endosomes to specialized insulin-regulated vesicles.
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DOI：
10.1091/mbc.e10-02-0158
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发表时间：
2010-06-15
影响因子：
3.3
通讯作者：
McGraw TE
中科院分区：
文献类型：
--
作者：
Jordens I;Molle D;Xiong W;Keller SR;McGraw TE
IRAP通过控制从内体到专门的胰岛素调节囊泡的分选，是GLUT 4运输的关键调节因子。胰岛素通过调节GLUT 4葡萄糖转运蛋白从细胞内区室到质膜的易位来刺激葡萄糖摄取。在不存在胰岛素的情况下，GLUT4被主动地从一般内体隔离到GLUT4专门化的隔室中，从而控制质膜上GLUT4的量。在这里，我们研究了氨基肽酶IRAP在GLUT 4运输中的作用。在未受刺激的IRAP敲低脂肪细胞中，由于胞吐作用增加，质膜GLUT4水平升高，表明IRAP在GLUT4保留中的重要作用。目前的证据支持这样的模型，即基础GLUT 4保留所需的AS160 RabGAP通过与IRAP的相互作用被募集到GLUT 4区室。然而，在这里，我们表明，AS160招募到GLUT4区室和AS160调节GLUT4运输不受IRAP敲低的影响。这些结果表明，AS160通过IRAP独立机制募集到膜上。与独立于AS160的作用一致，我们表明IRAP在GLUT4从内体分选到GLUT4专用区室中起作用。这通过在IRAP敲低细胞中GLUT 4重新定位至内体来揭示。虽然IRAP敲除对GLUT 4流量有深远的影响，但GLUT 4敲除不影响IRAP流量，表明IRAP流量独立于GLUT 4。总之，我们表明，IRAP是货物和胰岛素调节途径的关键调节剂。
IRAP is a key regulator of GLUT4 trafficking by controlling sorting from endosomes to specialized insulin-regulated vesicles. 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.
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影响因子：
5.3
作者：
Govers, R;Coster, ACF;James, DE
通讯作者：
James, DE
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29
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Eguez, L;Lee, A;McGraw, TE
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McGraw, TE
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通讯作者：
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通讯作者：
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作者：
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