Scholarlink

<p>The endoplasmic reticulum (ER) plays crucial roles in maintaining protein quality control and regulating dynamic Ca<sup>2+</sup> storage in eukaryotic cells. However, the proteostasis system involved in ER-mediated protein quality control has not been fully characterized. Here we show that Ca<sup>2+</sup> triggers the condensation of PDIA6, an ER-resident disulfide isomerase and molecular chaperone, into quality control granules. In contrast to the condensation mechanism observed for proteins containing low-complexity domains, our results indicate that transient but specific electrostatic interactions occur between the first and the third folded thioredoxin-like domains of PDIA6. We further show that the PDIA6 condensates recruit proinsulin, thereby accelerating the oxidative proinsulin folding and suppressing the proinsulin aggregation inside quality control granules, essential for secretion of insulin.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Ca2+-driven PDIA6 biomolecular condensation ensures proinsulin folding

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月11日

查看全文
  • Young-Ho Lee,
  • Tomohide Saio,
  • Mai Watabe,
  • Motonori Matsusaki,
  • Shingo Kanemura,
  • Yuxi Lin,
  • Taro Mannen,
  • Tsubura Kuramochi,
  • Yuka Kamada,
  • Katsuya Iuchi,
  • Michiko Tajiri,
  • Kotono Suzuki,
  • Yan Li,
  • Yunseok Heo,
  • Kotone Ishii,
  • Kenta Arai,
  • Kazunori Ban,
  • Mayuko Hashimoto,
  • Shuichiro Oshita,
  • Satoshi Ninagawa,
  • Yoshikazu Hattori,
  • Hiroyuki Kumeta,
  • Airu Takeuchi,
  • Shinji Kajimoto,
  • Hiroya Abe,
  • Eiichiro Mori,
  • Takahiro Muraoka,
  • Takakazu Nakabayashi,
  • Satoko Akashi,
  • Tsukasa Okiyoneda,
  • Michele Vendruscolo,
  • Kenji Inaba,
  • Masaki Okumura

摘要

The endoplasmic reticulum (ER) plays crucial roles in maintaining protein quality control and regulating dynamic Ca2+ storage in eukaryotic cells. However, the proteostasis system involved in ER-mediated protein quality control has not been fully characterized. Here we show that Ca2+ triggers the condensation of PDIA6, an ER-resident disulfide isomerase and molecular chaperone, into quality control granules. In contrast to the condensation mechanism observed for proteins containing low-complexity domains, our results indicate that transient but specific electrostatic interactions occur between the first and the third folded thioredoxin-like domains of PDIA6. We further show that the PDIA6 condensates recruit proinsulin, thereby accelerating the oxidative proinsulin folding and suppressing the proinsulin aggregation inside quality control granules, essential for secretion of insulin.