The septin cytoskeleton is required for plasma membrane repair.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2024-09-01 Epub Date: 2024-07-05 DOI:10.1038/s44319-024-00195-6

M Isabella Prislusky, Jonathan G T Lam, Viviana Ruiz Contreras, Marilynn Ng, Madeline Chamberlain, Sarika Pathak-Sharma, Madalyn Fields, Xiaoli Zhang, Amal O Amer, Stephanie Seveau

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Abstract

Plasma membrane repair is a fundamental homeostatic process of eukaryotic cells. Here, we report a new function for the conserved cytoskeletal proteins known as septins in the repair of cells perforated by pore-forming toxins or mechanical disruption. Using a silencing RNA screen, we identified known repair factors (e.g. annexin A2, ANXA2) and novel factors such as septin 7 (SEPT7) that is essential for septin assembly. Upon plasma membrane injury, the septin cytoskeleton is extensively redistributed to form submembranous domains arranged as knob and loop structures containing F-actin, myosin IIA, S100A11, and ANXA2. Formation of these domains is Ca²⁺-dependent and correlates with plasma membrane repair efficiency. Super-resolution microscopy revealed that septins and F-actin form intertwined filaments associated with ANXA2. Depletion of SEPT7 prevented ANXA2 recruitment and formation of submembranous actomyosin domains. However, ANXA2 depletion had no effect on domain formation. Collectively, our data support a novel septin-based mechanism for resealing damaged cells, in which the septin cytoskeleton plays a key structural role in remodeling the plasma membrane by promoting the formation of SEPT/F-actin/myosin IIA/ANXA2/S100A11 repair domains.

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质膜修复需要 septin 细胞骨架。

质膜修复是真核细胞的基本平衡过程。在这里，我们报告了被称为隔膜蛋白的保守细胞骨架蛋白在修复被孔形成毒素或机械破坏穿孔的细胞中的新功能。通过沉默 RNA 筛选，我们发现了已知的修复因子（如附件蛋白 A2、ANXA2）和新型因子，如隔蛋白 7（SEPT7），它对隔蛋白的组装至关重要。质膜损伤后，septin 细胞骨架广泛重新分布，形成膜下结构域，排列成包含 F-肌动蛋白、肌球蛋白 IIA、S100A11 和 ANXA2 的旋钮和环状结构。这些结构域的形成依赖于 Ca2+，并与质膜修复效率相关。超分辨率显微镜显示，隔膜蛋白和 F-肌动蛋白形成与 ANXA2 相关的交织丝。SEPT7 的缺失阻止了 ANXA2 的招募和膜下肌动蛋白结构域的形成。然而，ANXA2 的缺失对结构域的形成没有影响。总之，我们的数据支持一种基于septin的修复受损细胞的新机制，其中septin细胞骨架通过促进SEPT/F-肌动蛋白/肌球蛋白IIA/ANXA2/S100A11修复域的形成，在重塑质膜方面发挥了关键的结构作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.