The KDEL receptor and vesicular traffic

• Project/Area Number: 12680684
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: CHIBA UNIVERSITY
• Principal Investigator: AOE Tomohiko Chiba Univeiisity, Graduate School of Medicine, Molecular Embryology, assistant professor, 大学院・医学研究院, 助教授 (90311612)
• Co-Investigator(Kenkyū-buntansha): KOSEKI Haruhiko Chiba Univeiisity, Graduate School of Medicine, Molecular Embryology, professor, 大学院・医学研究院, 教授 (40225446)
• Project Period (FY): 2000 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000); Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: KDEL receptor / Golgi / ER / chaperone / COPI / COPI

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)