Stochastic contraction of myosin minifilaments drives evolution of microridge protrusion patterns in epithelial cells.
Stochastic contraction of myosin minifilaments drives evolution of microridge protrusion patterns in epithelial cells.
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DOI：
10.1091/mbc.e21-05-0258
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发表时间：
2021-08-01
影响因子：
3.3
通讯作者：
Sagasti A
中科院分区：
文献类型：
--
作者：
van Loon AP;Erofeev IS;Goryachev AB;Sagasti A
基于肌动蛋白的突起在形态、稳定性和细胞表面的排列方面各不相同。微脊是粘膜上皮细胞上横向伸长的突起，它们形成均匀间隔的迷宫状图案，通过裂变和融合动态重塑。为了表征微脊如何形成高度有序的亚细胞模式并研究驱动裂变和融合的机制，我们对斑马鱼幼虫成熟皮肤中的微脊进行了成像。经过最初的发展，微脊的间距和排列变得越来越有序。 F-肌动蛋白和非肌肉肌球蛋白 II (NMII) 成像显示微脊裂变和融合与顶皮质局部 NMII 活性相关。抑制 NMII 可阻止裂变和融合重排、降低微脊密度并改变微脊间距。高分辨率成像使我们能够对活体动物细胞顶皮层中的单个 NMII 微丝进行成像，揭示微丝被束缚在突起上，并且通常连接相邻的微脊。连接两个微脊末端的 NMII 微丝将它们融合在一起，而垂直于微脊定向的微丝将它们切断或将它们拉得更近。这些发现表明，随着细胞成熟，皮质 NMII 活动会协调重塑过程，从而形成越来越有序的微脊排列。
Actin-based protrusions vary in morphology, stability, and arrangement on cell surfaces. Microridges are laterally elongated protrusions on mucosal epithelial cells, where they form evenly spaced, mazelike patterns that dynamically remodel by fission and fusion. To characterize how microridges form their highly ordered, subcellular patterns and investigate the mechanisms driving fission and fusion, we imaged microridges in the maturing skin of zebrafish larvae. After their initial development, microridge spacing and alignment became increasingly well ordered. Imaging F-actin and non-muscle myosin II (NMII) revealed that microridge fission and fusion were associated with local NMII activity in the apical cortex. Inhibiting NMII blocked fission and fusion rearrangements, reduced microridge density, and altered microridge spacing. High-resolution imaging allowed us to image individual NMII minifilaments in the apical cortex of cells in live animals, revealing that minifilaments are tethered to protrusions and often connect adjacent microridges. NMII minifilaments connecting the ends of two microridges fused them together, whereas minifilaments oriented perpendicular to microridges severed them or pulled them closer together. These findings demonstrate that as cells mature, cortical NMII activity orchestrates a remodeling process that creates an increasingly orderly microridge arrangement.