Gurdon Institute, University of Cambridge, Cambridge, UK.
Department of Biochemistry, University of Cambridge, Cambridge, UK.
J Cell Biol. 2021 Apr 5;220(4). doi: 10.1083/jcb.202003052.
Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways.
肌动蛋白及其调节蛋白的组装构成了所有真核细胞动态形态的基础。为了了解肌动蛋白调节蛋白如何协同作用产生富含肌动蛋白的结构，如丝状伪足，我们分析了果蝇胚胎中的丝状伪足和类似丝状伪足的体外系统（FLS）中不同肌动蛋白调节蛋白的定位。我们发现，肌动蛋白结合的调节蛋白复合物的组成（丝状伪足尖端复合物）在体内和体外都非常不均匀。我们的数据表明，不同的蛋白质对与彼此以及与肌动蛋白束长度相关，表明存在功能亚复合物。这与一个理论框架一致，即三个或更多冗余的亚复合物随机加入尖端复合物，其中任何两个都足以驱动丝状伪足的形成。我们对观察到的异质性提供了一个解释，并表明基于多个组件的机制允许从不同的上游信号通路产生典型的丝状伪足动力学。
