The KDEL receptor and vesicular traffic

KDEL 受体和囊泡交通

• 批准号: 12680684
• 负责人: AOE Tomohiko
• 金额: $ 2.37万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680684/
• 关键词: KDEL receptor; Golgi; ER; chaperone; COPI; COPI

Newly synthesized proteins in the endoplasmic reticulum (ER) must fold and assemble correctly before being transported to their final cellular destination. While some misfolded or partially assembled proteins have been shown to exit the ER, they fail to escape the early secretory system entirely, because they are retrieved from post-ER compartments to the ER. We elucidate a mechanistic basis for this retrieval and characterize its contribution to ER quality control by studying the fate of the unassembled T cell antigen receptor (TCR) α chain. While the steady-state distribution of TCRα is in the ER, inhibition of retrograde transport by COPI induces the accumulation of TCRα in post-ER compartments, suggesting that TCRα is cycling between the ER and post-ER compartments. TCRα associates with BiP, a KDEL protein. Disruption of the ligand-binding function of the KDEL receptor releases TCRα from the early secretory system to the cell surface, so that TCRα is no longer subject to ER degradation. Thus, our findings suggest that retrieval by the KDEL receptor contributes to mechanisms by which the ER monitors newly synthesized proteins for their proper disposal.

内质网（ER）中新合成的蛋白质在被运输到最终的细胞目的地之前必须正确折叠和组装。虽然一些错误折叠或部分组装的蛋白质已被证明可以退出内质网，但它们不能完全逃离早期分泌系统，因为它们从内质网后的室室被回收到内质网。我们阐明了这种检索的机制基础，并通过研究未组装的T细胞抗原受体(TCR) α链的命运来表征其对内质网质量控制的贡献。虽然TCRα的稳态分布在内质网中，但通过COPI抑制逆行转运诱导了TCRα在内质网后腔室的积累，这表明TCRα在内质网和内质网后腔室之间循环。TCRα与KDEL蛋白BiP相关。破坏KDEL受体的配体结合功能将TCRα从早期分泌系统释放到细胞表面，使TCRα不再受到内质网降解。因此，我们的研究结果表明，KDEL受体的检索有助于内质网监测新合成蛋白的适当处理机制。

项目成果

Yamamoto, K., Fujii, R., Toyofuku.Y., Saito, T., Koseki, H., Hsu, VW., Aoe, T.: "The KDEL receptor mediates a retrieval mechanism that contributes to quality control at the endoplasmic reticulum"EMBO J. 20. 3082-3091 (2001)

Yamamoto, K.、Fujii, R.、Toyofuku.Y.、Saito, T.、Koseki, H.、Hsu, VW.、Aoe, T.：“KDEL 受体介导一种检索机制，有助于质量控制

Yamamoto, K., et al.: "The KDEL receptor mediates a retrieval mechanism that contributes to quality control at the endoplasmic reticulum"EMBO J.. 20. 3082-3091 (2001)

Yamamoto, K. 等人：“KDEL 受体介导有助于内质网质量控制的恢复机制”EMBO J.. 20. 3082-3091 (2001)

Yamamoto, K., Fujii, R., Toyofuku, Y., Saito, T., Koseki, H., HSu, VW., Aoe, T.: "The KDEL receptpr mediates a retrieval mechanism that contributes to quality control at the endoplashiic reticulum"EMBO J 20. 3082-3091 (2001)

Yamamoto, K.、Fujii, R.、Toyofuku, Y.、Saito, T.、Koseki, H.、HSu, VW.、Aoe, T.：“KDEL 受体介导一种检索机制，有助于质量控制