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CYRI 控制果蝇表皮伤口闭合和侵袭性边缘细胞簇的黏附。

CYRI controls epidermal wound closure and cohesion of invasive border cell cluster in Drosophila.

机构信息

Department of Molecular Cell Physiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, Marburg, Germany.

出版信息

J Cell Biol. 2024 Dec 2;223(12). doi: 10.1083/jcb.202310153. Epub 2024 Oct 25.

DOI:10.1083/jcb.202310153
PMID:39453414
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11519390/
Abstract

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.

摘要

细胞迁移对于许多生物学过程至关重要，包括形态发生、伤口愈合和癌症侵袭。WAVE 调节复合物 (WRC) 是一种中央 Arp2/3 调节剂，可在 Rac GTPase 激活后驱动细胞迁移。CYFIP 相关 Rac1 相互作用蛋白 (CYRI) 被认为与 WRC 竞争与 Rac1 的相互作用，形成反馈环以调节片状伪足动力学。然而，CYRI 蛋白在健康组织中的生理作用在体内尚不清楚。在这里，我们使用果蝇作为模型系统来研究 CYRI 在细胞和机体水平上的功能。我们发现，CYRI 不仅是控制片状伪足扩展的单个巨噬细胞中强有力的 WRC 调节剂，而且还确定 CYRI 是 Rac-WRC-Arp2/3 途径的分子制动器，可减缓表皮伤口愈合。此外，我们发现 CYRI 通过控制簇内聚力和迁移来限制侵袭性边界细胞的迁移。因此，我们的数据强调了 CYRI 作为一种重要的细胞和上皮组织动力学调节剂，在不同物种中具有保守性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/99c173c2e10b/JCB_202310153_Fig8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/a33b15f3fcff/JCB_202310153_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/16c85db85e44/JCB_202310153_FigS3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/99c173c2e10b/JCB_202310153_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/527aede6f5a5/JCB_202310153_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/aa4ef80d22fd/JCB_202310153_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/c91810b171ad/JCB_202310153_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/b4662aea4e54/JCB_202310153_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/db6f7767c82e/JCB_202310153_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/2d137f3114d9/JCB_202310153_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/a33b15f3fcff/JCB_202310153_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/16c85db85e44/JCB_202310153_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/224f80d49dba/JCB_202310153_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/faaaea4f3404/JCB_202310153_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/200cd755eef6/JCB_202310153_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7330/11519390/99c173c2e10b/JCB_202310153_Fig8.jpg

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