The ABCA1 Q597R mutant undergoes trafficking from the ER upon ER stress.
The ABCA1 Q597R mutant undergoes trafficking from the ER upon ER stress.
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DOI：
10.1016/j.bbrc.2008.03.018
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发表时间：
2008-05
影响因子：
3.1
通讯作者：
Arowu R. Tanaka;F. Kano;K. Ueda;M. Murata
中科院分区：
文献类型：
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作者：
Arowu R. Tanaka;F. Kano;K. Ueda;M. Murata
ATP 结合盒转运蛋白 1 (ABCA1)（一种与细胞胆固醇流出相关的膜蛋白）的突变会导致丹吉尔病 (TD)。之前，我们证明了 TD 中鉴定的 ABCA1 Q597R 突变体 (QR) 保留在内质网中。在这里，我们报道了毒胡萝卜素或 DTT 快速诱导 QR 运输到质膜，这表明 ER 应激诱导 QR 运输。然而，没有观察到 ABCA1 活性的药理学救援。贩运依赖于 COPII 成分，并通过 ER-高尔基体中间室发生。此外，我们发现 QR 对 ER 应激比 ATF6（一种与 ER 应激反应相关的转录因子）更敏感。这些结果表明毒胡萝卜素可以有效纠正运输缺陷，并提出内质网应激诱导的运输参与内质网质量控制的可能性。
Mutations in ATP binding cassette transporter 1 (ABCA1), a membrane protein associated with cellular cholesterol efflux, cause Tangier disease (TD). Previously, we showed that an ABCA1 Q597R mutant (QR) identified in TD is retained in the endoplasmic reticulum. Here, we report that QR trafficking to the plasma membrane was rapidly induced by thapsigargin or DTT, indicating that ER stress-induced QR trafficking. However, pharmacological rescue of ABCA1 activity was not observed. The trafficking was dependent on COPII components and occurred via the ER-Golgi intermediate compartments. Furthermore, we found that QR was more sensitive to ER stress than ATF6, a transcription factor associated with the ER stress response. These results suggest that thapsigargin can be effective in correcting trafficking defects, and raise the possibility that ER stress-induced trafficking is involved in ER quality control.