CYRI控制果蝇表皮伤口闭合和侵入性边界细胞簇的内聚。

IF 7.4 1区 生物学 Q1 CELL BIOLOGY Journal of Cell Biology Pub Date : 2024-10-25 DOI:10.1083/jcb.202310153
Marvin Rötte,Mila Y Höhne,Dennis Klug,Kirsten Ramlow,Caroline Zedler,Franziska Lehne,Meike Schneider,Maik C Bischoff,Sven Bogdan
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引用次数: 0

摘要

细胞运动对形态发生、伤口愈合和癌症侵袭等许多生物过程至关重要。WAVE 调节复合体(WRC)是一个中心 Arp2/3 调节器,在 Rac GTPase 激活的下游驱动细胞运动。CYFIP相关Rac1互作因子(CYRI)蛋白被认为在调节片层动态的反馈环中与WRC竞争与Rac1的互作。然而,CYRI 蛋白在体内健康组织中的生理作用尚不清楚。在这里,我们以果蝇为模型系统,研究 CYRI 在细胞和机体水平上的功能。我们发现,CYRI 不仅在单个巨噬细胞中是一种强效的 WRC 调节器,可控制薄片扩散,而且还发现 CYRI 是 Rac-WRC-Arp2/3 通路的分子制动器,可减缓表皮伤口愈合。此外,我们还发现,CYRI 通过控制集群的凝聚和迁移,限制了侵袭性边界细胞的迁移。因此,我们的数据突出表明,CYRI 是细胞和上皮组织动态的重要调节因子,在不同物种之间是一致的。
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CYRI controls epidermal wound closure and cohesion of invasive border cell cluster in Drosophila.
Cell motility is crucial for many biological processes including morphogenesis, wound healing, and cancer invasion. The WAVE regulatory complex (WRC) is a central Arp2/3 regulator driving cell motility downstream of activation by Rac GTPase. CYFIP-related Rac1 interactor (CYRI) proteins are thought to compete with WRC for interaction with Rac1 in a feedback loop regulating lamellipodia dynamics. However, the physiological role of CYRI proteins in vivo in healthy tissues is unclear. Here, we used Drosophila as a model system to study CYRI function at the cellular and organismal levels. We found that CYRI is not only a potent WRC regulator in single macrophages that controls lamellipodial spreading but also identified CYRI as a molecular brake on the Rac-WRC-Arp2/3 pathway to slow down epidermal wound healing. In addition, we found that CYRI limits invasive border cell migration by controlling cluster cohesion and migration. Thus, our data highlight CYRI as an important regulator of cellular and epithelial tissue dynamics conserved across species.
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来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
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