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.

中文翻译：

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CYRI 控制果蝇中表皮伤口闭合和侵袭性边界细胞簇的凝聚。


细胞运动对于许多生物过程至关重要，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 调节因子，可驱动 Rac GTP 酶激活下游的细胞运动。CYFIP 相关 Rac1 相互作用器 （CYRI） 蛋白被认为在调节板状伪足动力学的反馈回路中与 WRC 竞争与 Rac1 的相互作用。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，我们使用果蝇作为模型系统来研究细胞和生物水平的 CYRI 功能。我们发现 CYRI 不仅是单个巨噬细胞中控制板状足部扩散的有效 WRC 调节剂，而且还将 CYRI 确定为 Rac-WRC-Arp2/3 通路上的分子制动器，以减缓表皮伤口愈合。此外，我们发现 CYRI 通过控制簇凝聚力和迁移来限制侵袭性边界细胞迁移。因此，我们的数据突出了 CYRI 是跨物种保守的细胞和上皮组织动力学的重要调节因子。