Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of Life Sciences and Ministry of Education Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37). doi: 10.1073/pnas.2100805118.
The formation of the branched actin networks is essential for cell polarity, but it remains unclear how the debranching activity of actin filaments contributes to this process. Here, we showed that an evolutionarily conserved coronin family protein, the POD-1, debranched the Arp2/3-nucleated actin filaments in vitro. By fluorescence live imaging analysis of the endogenous POD-1 protein, we found that POD-1 colocalized with Arp2/3 at the leading edge of the migrating neuroblasts. Conditional mutations of POD-1 in neuroblasts caused aberrant actin assembly, disrupted cell polarity, and impaired cell migration. In one-cell-stage embryos, POD-1 and Arp2/3, moved together during cell polarity establishment, and inhibition of POD-1 blocked Arp2/3 motility and affected the polarized cortical flow, leading to symmetric segregation of cell fate determinants. Together, these results indicate that F-actin debranching organizes actin network and cell polarity in migrating neuroblasts and asymmetrically dividing embryos.
分支肌动蛋白网络的形成对于细胞极性至关重要,但目前尚不清楚肌动蛋白丝的去分支活性如何促进这一过程。在这里,我们表明,一种进化上保守的 coronin 家族蛋白,POD-1,在体外使 Arp2/3 成核的肌动蛋白丝去分支。通过对内源性 POD-1 蛋白的荧光活细胞成像分析,我们发现 POD-1 在迁移神经母细胞的前缘与 Arp2/3 共定位。神经母细胞中 POD-1 的条件突变导致肌动蛋白组装异常,破坏细胞极性,并损害细胞迁移。在单细胞期胚胎中,POD-1 和 Arp2/3 在建立细胞极性期间一起移动,抑制 POD-1 阻断了 Arp2/3 的运动,并影响了极化的皮层流,导致细胞命运决定因素的对称分离。总之,这些结果表明 F-肌动蛋白的去分支在迁移的神经母细胞和不对称分裂的胚胎中组织肌动蛋白网络和细胞极性。