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<p>Newly synthesized secretory proteins and lipids are transported from the endoplasmic reticulum (ER) to the Golgi prior to their ultimate destinations, which is tightly regulated during adaptation to environmental stress. However, regulatory pathways governing the formation of COPII vesicles budded from the ER remain insufficiently explored. Here, we present evidence indicating that COPII-mediated vesicle transport is transcriptionally controlled through the phosphatidic acid (PA)-dependent Opi1-Ino2/Ino4 regulatory circuit. Our analysis shows that <i>YIP3</i>, a target gene of Ino2/Ino4, exerts a negative regulatory impact on COPII-mediated vesicle transport. We demonstrate that Ino2/Ino4, but not Yip3 modulates Sar1 activation, the initial step in COPII vesicle formation, whereas Yip3 hinders Sec16 assembly on the ER membrane, thereby implying that Ino2/Ino4 governs COPII vesicle formation at multiple steps. Finally, we show that under ER stress conditions which are accompanied by elevated PA, vesicular transport is restricted in a PA and Yip3-dependent manner. Thus, this study provides the first evidence for an ER sensing system that transcriptionally fine-tunes vesicle formation in response to alterations in lipid composition of the ER membrane during ER stress.</p>

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ER sensing of lipid metabolism drives PRA family-dependent regulation of COPII vesicle transport

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月3日

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  • Kazuki Hanaoka,
  • Mitsuki Nakazato,
  • Philipp Schlarmann,
  • Hiroki Nakamura,
  • Mei Kato,
  • Ryoko Ikema,
  • Mizuki Iguchi,
  • Katsuki Eto,
  • Takefumi Karashima,
  • Atsuko Ikeda,
  • Yukari Yabuki,
  • Javier Manzano-Lopez,
  • Auxiliadora Aguilera-Romero,
  • Susana Sabido-Bozo,
  • Ana Maria Perez-Linero,
  • Muneyoshi Kanai,
  • Haruyuki Iefuji,
  • Isabelle Riezman,
  • Howard Riezman,
  • Manuel Muñiz,
  • Kouichi Funato

摘要

Newly synthesized secretory proteins and lipids are transported from the endoplasmic reticulum (ER) to the Golgi prior to their ultimate destinations, which is tightly regulated during adaptation to environmental stress. However, regulatory pathways governing the formation of COPII vesicles budded from the ER remain insufficiently explored. Here, we present evidence indicating that COPII-mediated vesicle transport is transcriptionally controlled through the phosphatidic acid (PA)-dependent Opi1-Ino2/Ino4 regulatory circuit. Our analysis shows that YIP3, a target gene of Ino2/Ino4, exerts a negative regulatory impact on COPII-mediated vesicle transport. We demonstrate that Ino2/Ino4, but not Yip3 modulates Sar1 activation, the initial step in COPII vesicle formation, whereas Yip3 hinders Sec16 assembly on the ER membrane, thereby implying that Ino2/Ino4 governs COPII vesicle formation at multiple steps. Finally, we show that under ER stress conditions which are accompanied by elevated PA, vesicular transport is restricted in a PA and Yip3-dependent manner. Thus, this study provides the first evidence for an ER sensing system that transcriptionally fine-tunes vesicle formation in response to alterations in lipid composition of the ER membrane during ER stress.