Protein quality control mechanisms in the early secretory pathway mediated by ERp44 and zinc transporters

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16065
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Tohoku University
• Principal Investigator: Amagai Yuta 東北大学, 多元物質科学研究所, 助教 (90773896)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ERp44 / 亜鉛輸送体 / 亜鉛 / 初期分泌経路 / ゴルジ体 / 小胞体 / タンパク質品質管理

Outline of Final Research Achievements

Newly synthesized secretory proteins are natively folded in the early secretory pathway: the endoplasmic reticulum and the Golgi apparatus. These organelles contain a number of systems to survey the quality of these proteins. We had found that zinc ions play a crucial role in this protein quality control system via an activation of ERp44, a member of PDI family.
In this study, newly developed zinc imaging technology revealed how zinc transporters involve in the regulation of zinc homeostasis at the Golgi apparatus. Knockdown of the Golgi-localized zinc transporters induced malfunction of ERp44-mediated protein quality control in the early secretory pathway.

Free Research Field

生体機能化学

Academic Significance and Societal Importance of the Research Achievements

これまで、小胞体ゴルジ体内の亜鉛濃度がどのくらいであるかはほとんど不明であった。私たちが開発した手法により、その値が明らかとなった。さらに亜鉛輸送体がどのように亜鉛濃度維持に関わっているかを発見することができた。これらの研究成果は、分泌経路における亜鉛の生理的な意義を考える上で重要な基礎的知見になると考えられ、本研究成果をもとに亜鉛生物学の発展に大きく寄与すると考えられる。