Department of Biology, The University of Massachusetts Amherst, Amherst, MA.
J Cell Biol. 2020 Nov 2;219(11). doi: 10.1083/jcb.202007158.
Much of our understanding of actin-driven phenotypes in eukaryotes has come from the "yeast-to-human" opisthokont lineage and the related amoebozoa. Outside of these groups lies the genus Naegleria, which shared a common ancestor with humans >1 billion years ago and includes the "brain-eating amoeba." Unlike nearly all other known eukaryotic cells, Naegleria amoebae lack interphase microtubules; this suggests that actin alone drives phenotypes like cell crawling and phagocytosis. Naegleria therefore represents a powerful system to probe actin-driven functions in the absence of microtubules, yet surprisingly little is known about its actin cytoskeleton. Using genomic analysis, microscopy, and molecular perturbations, we show that Naegleria encodes conserved actin nucleators and builds Arp2/3-dependent lamellar protrusions. These protrusions correlate with the capacity to migrate and eat bacteria. Because human cells also use Arp2/3-dependent lamellar protrusions for motility and phagocytosis, this work supports an evolutionarily ancient origin for these processes and establishes Naegleria as a natural model system for studying microtubule-independent cytoskeletal phenotypes.
我们对真核生物肌动蛋白驱动表型的了解很大程度上来自于“酵母到人”后生动物谱系和相关的变形虫。在这些群体之外是内格里亚属，它与人类的共同祖先可以追溯到 10 亿多年前，包括“食脑变形虫”。与几乎所有其他已知的真核细胞不同，内格里亚变形虫缺乏间期中的微管；这表明肌动蛋白单独驱动细胞爬行和吞噬等表型。因此，内格里亚属代表了一个在没有微管的情况下研究肌动蛋白驱动功能的强大系统，但令人惊讶的是，人们对内格里亚属的肌动蛋白细胞骨架知之甚少。通过基因组分析、显微镜观察和分子扰动，我们表明内格里亚属编码保守的肌动蛋白成核因子，并构建 Arp2/3 依赖性片状突起。这些突起与迁移和吞噬细菌的能力相关。因为人类细胞也使用 Arp2/3 依赖性片状突起进行运动和吞噬作用，所以这项工作支持这些过程具有古老的进化起源，并确立了内格里亚属作为研究微管非依赖性细胞骨架表型的天然模型系统。
