CHMP2A的缺失与细胞动力学脱落过程中ESCRT-III蛋白的有序组装有关。

IF 2.7 3区 生物学 Q3 CELL BIOLOGY
Nikita Kamenetsky, Dikla Nachmias, Suman Khan, Ori Avinoam, Itay Hazan, Alexander Upcher, Natalie Elia
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引用次数: 0

摘要

ESCRT机制介导基本细胞过程中的膜重塑,包括细胞质分裂、内体分选、核膜重构和膜修复。膜的收缩和断裂是由成丝的ESCRT-III复合体和aaa - atp酶VPS4驱动的。虽然escrt - iii驱动的膜断裂已被普遍建立,但其12种哺乳动物同种异构体在细胞中的组装和协调机制仍知之甚少。在这里,我们通过消耗ESCRT-III的核心成分CHMP2A,研究了哺乳动物细胞动力学脱落过程中ESCRT-III亚基的空间组织和相互依赖性。利用活细胞成像、结构照明显微镜(SIM)和相关的光电子显微镜(CLEM),我们发现CHMP2A敲除细胞在脱落过程中表现出明显的延迟(而不是失败),同时在ESCRT-III亚基中存在明显的错定位表型。虽然IST1和CHMP2B的破坏程度最低,但CHMP4B、CHMP3和CHMP1B在脱落部位表现出逐渐严重的组织缺陷。双蛋白成像显示,在单个chmp2a缺陷细胞中,ESCRT-III亚基之间的协调被破坏,支持细胞动力学脱落中ESCRT-III亚基的有序组装。总之,我们的研究结果首次提供了ESCRT-III亚基在escrt介导的膜重构过程中的分层组装的体内证据,并确定了CHMP2A是ESCRT-III结构的关键组织者,对及时的膜脱落至关重要。[媒体:见文][媒体:见文]。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Loss of CHMP2A implicates an ordered assembly of ESCRT-III proteins during cytokinetic abscission.

The ESCRT machinery mediates membrane remodeling in fundamental cellular processes including cytokinesis, endosomal sorting, nuclear envelope reformation, and membrane repair. Membrane constriction and scission is driven by the filament-forming ESCRT-III complex and the AAA-ATPase VPS4. While ESCRT-III-driven membrane scission is generally established, the mechanisms governing the assembly and coordination of its twelve mammalian isoforms in cells remain poorly understood. Here, we examined the spatial organization and interdependence of ESCRT-III subunits during mammalian cytokinetic abscission by depleting CHMP2A, a core ESCRT-III component. Using live cell imaging, structured illumination microscopy (SIM) and correlative light-electron microscopy (CLEM), we show that CHMP2A knockout cells display a significant delay-but not failure-in abscission, accompanied by distinct mislocalization phenotypes across ESCRT-III subunits. While IST1 and CHMP2B were minimally disrupted, CHMP4B, CHMP3, and CHMP1B display progressively severe organization defects at the abscission site. Dual-protein imaging reveals disrupted coordination between ESCRT-III subunits in individual CHMP2A-deficient cells, supporting an ordered assembly of ESCRT-III subunits in cytokinetic abscission. Together, our findings provide the first in vivo evidence for hierarchical assembly of ESCRT-III subunits during ESCRT-mediated membrane remodeling and identify CHMP2A as a key organizer of ESCRT-III architecture essential for timely membrane abscission. [Media: see text] [Media: see text].

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来源期刊
Molecular Biology of the Cell
Molecular Biology of the Cell 生物-细胞生物学
CiteScore
6.00
自引率
6.10%
发文量
402
审稿时长
2 months
期刊介绍: MBoC publishes research articles that present conceptual advances of broad interest and significance within all areas of cell, molecular, and developmental biology. We welcome manuscripts that describe advances with applications across topics including but not limited to: cell growth and division; nuclear and cytoskeletal processes; membrane trafficking and autophagy; organelle biology; quantitative cell biology; physical cell biology and mechanobiology; cell signaling; stem cell biology and development; cancer biology; cellular immunology and microbial pathogenesis; cellular neurobiology; prokaryotic cell biology; and cell biology of disease.
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