Micron-scale supramolecular myosin arrays help mediate cytoskeletal assembly at mature adherens junctions.
Micron-scale supramolecular myosin arrays help mediate cytoskeletal assembly at mature adherens junctions.
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DOI：
10.1083/jcb.202103074
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发表时间：
2022-01-03
期刊：
影响因子：
--
通讯作者：
Peifer M
中科院分区：
文献类型：
--
作者：
Yu-Kemp HC;Szymanski RA;Cortes DB;Gadda NC;Lillich ML;Maddox AS;Peifer M
Yu-Kemp等人。探索上皮细胞在基于E-钙粘附素的细胞-细胞连接处组装超分子肌动球蛋白结构的机制。他们发现，单个肌动蛋白组装途径并不是必不可少的。取而代之的是，显微镜和药物抑制表明，微米级超分子肌球蛋白阵列有助于在成熟连接处捆绑肌动蛋白。上皮细胞在基于E-钙粘附素的细胞-细胞连接处组装特殊的肌动球蛋白结构，在形态发生过程中所施加的力驱动细胞形状的改变。构建这种超分子肌动球蛋白结构的机制尚不清楚。我们使用了ZO击倒MDCK细胞，它在Zonula粘连处组装了一个强大的、极化的和高度组织化的肌球蛋白细胞骨架，结合遗传和药理学方法与超分辨显微镜来定义所需的分子机器。令我们惊讶的是，抑制单个肌动蛋白组装途径(Arp2/3、Forins或Ena/Vasp)并没有阻止或推迟这种极化的肌动球蛋白结构的组装。相反，随着连接的成熟，微米级超分子肌球蛋白阵列组装在一起，与顶膜相邻的排列成堆的肌球蛋白细丝覆盖在杂乱无章的肌动蛋白细丝上。这表明肌球蛋白阵列可能在成熟的连接处捆绑肌动蛋白。与这一想法一致的是，抑制ROCK或肌球蛋白ATPase会扰乱肌球蛋白的定位/组织，并阻止肌动蛋白捆绑和极化。我们在Caco-2细胞中获得了类似的结果。这些结果表明了肌球蛋白自组装的新作用，有助于推动肌动蛋白的组织促进细胞形状的改变。
Yu-Kemp et al. explore mechanisms that epithelial cells use to assemble supramolecular actomyosin structures at E-Cadherin–based cell–cell junctions. They find that individual actin assembly pathways are not essential. Instead, microscopy and pharmacologic inhibition suggest that micron-scale supramolecular myosin arrays help bundle actin at mature junctions. Epithelial cells assemble specialized actomyosin structures at E-Cadherin–based cell–cell junctions, and the force exerted drives cell shape change during morphogenesis. The mechanisms that build this supramolecular actomyosin structure remain unclear. We used ZO-knockdown MDCK cells, which assemble a robust, polarized, and highly organized actomyosin cytoskeleton at the zonula adherens, combining genetic and pharmacologic approaches with superresolution microscopy to define molecular machines required. To our surprise, inhibiting individual actin assembly pathways (Arp2/3, formins, or Ena/VASP) did not prevent or delay assembly of this polarized actomyosin structure. Instead, as junctions matured, micron-scale supramolecular myosin arrays assembled, with aligned stacks of myosin filaments adjacent to the apical membrane, overlying disorganized actin filaments. This suggested that myosin arrays might bundle actin at mature junctions. Consistent with this idea, inhibiting ROCK or myosin ATPase disrupted myosin localization/organization and prevented actin bundling and polarization. We obtained similar results in Caco-2 cells. These results suggest a novel role for myosin self-assembly, helping drive actin organization to facilitate cell shape change.
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影响因子：
9.2
作者：
Ebrahim, Seham;Fujita, Tomoki;Millis, Bryan A.;Kozin, Elliott;Ma, Xuefei;Kawamoto, Sachiyo;Baird, Michelle A.;Davidson, Michael;Yonemura, Shigenobu;Hisa, Yasuo;Conti, Mary Anne;Adelstein, Robert S.;Sakaguchi, Hirofumi;Kachar, Bechara
通讯作者：
Kachar, Bechara
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DOI：
10.1016/j.cub.2015.02.012
发表时间：
2015-03-30
期刊：
Current biology : CB
影响因子：
--
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
3.3
作者：
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