2026-03-10 沖縄科学技術大学院大学
＜関連情報＞
- https://www.oist.jp/ja/news-center/news/2026/3/10/writing-catalog-plasma-membrane-repair-proteins
- https://elifesciences.org/reviewed-preprints/108585v1
- https://www.nature.com/articles/s43587-024-00575-6
細胞膜修復タンパク質の大規模同定により、細胞膜損傷に対する時空間的な細胞応答が明らかになった Large-scale identification of plasma membrane repair proteins revealed spatiotemporal cellular responses to plasma membrane damage
Yuta Yamazaki,Keiko Kono
eLife Reviewed Preprint v1:September 11, 2025
DOI:https://doi.org/10.7554/eLife.108585.1
Abstract
Damage to the plasma membrane (PM) is common in all types of cells. PM repair processes, including exocytosis and endocytosis, are not mutually exclusive; rather, they collaborate to repair the wound. However, the temporal coordination between the repair processes remains poorly understood. Here, by large-scale identification and live-cell imaging of PM repair proteins, we analyzed the spatiotemporal PM damage responses in Saccharomyces cerevisiae. Of the 80 repair proteins identified, 72 proteins were previously unreported repair protein candidates. Among the observed repair processes, the polarized exocytosis and clathrin-mediated endocytosis (CME) are coupled at the damage site, with exocytosis predominating in the early stage of PM repair and CME predominating in the late stage of PM repair. Furthermore, we showed that CME at the growing bud site directs PM repair proteins with transmembrane domains to the damage site. We propose a model in which CME delivers repair proteins with transmembrane domains between the growing bud site and the damage site. This study provides a functional catalog of PM repair proteins and insights into spatiotemporal cellular responses to PM damage.
細胞膜損傷は酵母の複製寿命を制限し、ヒト線維芽細胞の早期老化を誘導する Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts
Kojiro Suda,Yohsuke Moriyama,Nurhanani Razali,Yatzu Chiu,Yumiko Masukagami,Koutarou Nishimura,Hunter Barbee,Hiroshi Takase,Shinju Sugiyama,Yuta Yamazaki,Yoshikatsu Sato,Tetsuya Higashiyama,Yoshikazu Johmura,Makoto Nakanishi & Keiko Kono
Nature Aging Published:22 February 2024
DOI:https://doi.org/10.1038/s43587-024-00575-6
Abstract
Plasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. In this study, using budding yeast and normal human fibroblasts, we found that cellular senescence—stable cell cycle arrest contributing to organismal aging—is the long-term outcome of PMD. Our genetic screening using budding yeast unexpectedly identified a close genetic association between PMD response and replicative lifespan regulations. Furthermore, PMD limits replicative lifespan in budding yeast; upregulation of membrane repair factors ESCRT-III (SNF7) and AAA-ATPase (VPS4) extends it. In normal human fibroblasts, PMD induces premature senescence via the Ca2+–p53 axis but not the major senescence pathway, DNA damage response pathway. Transient upregulation of ESCRT-III (CHMP4B) suppressed PMD-dependent senescence. Together with mRNA sequencing results, our study highlights an underappreciated but ubiquitous senescent cell subtype: PMD-dependent senescent cells.
