Plectin linkages are mechanosensitive and required for the nuclear piston mechanism of three-dimensional cell migration.
Plectin linkages are mechanosensitive and required for the nuclear piston mechanism of three-dimensional cell migration.
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DOI：
10.1091/mbc.e21-08-0414
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发表时间：
2022-10-01
影响因子：
3.3
通讯作者：
Petrie, Ryan J.
中科院分区：
文献类型：
--
作者：
Marks, Pragati C.;Hewitt, Breanne R.;Baird, Michelle A.;Wiche, Gerhard;Petrie, Ryan J.
迁移通过生理学相关的三维（3D）基质（如细胞衍生基质（CDM））的细胞使用肌动球蛋白和波形蛋白中间丝向前拉动细胞核并对细胞前部加压，作为3D迁移的细胞核活塞机制的一部分。在这项研究中，我们测试了细胞骨架交联蛋白质plectin在促进细胞核通过3D矩阵的运动中的作用。我们发现，F-肌动蛋白和波形蛋白丝的相互作用，在二维玻璃和三维CDM细胞需要肌动球蛋白收缩。果胶还促进了这些相互作用，并与波形蛋白相互作用，以响应匪II收缩性和底物硬度，表明果胶和波形蛋白的关联是机械敏感的。我们发现，这种机械敏感的plectin复合物减缓了2D迁移，但对于将细胞核向前拉动并在3D CDM中产生区室化的细胞内压力以及3D胶原蛋白中的低压板层脂质迁移至关重要。最后，plectin的表达有助于将NMII定位在细胞核的前面，并将波形蛋白网络定位在细胞核周围。总之，我们的数据表明，网蛋白交联波形蛋白和肌动球蛋白丝，组织波形蛋白网络，并极化NMII，以促进三维细胞迁移的核活塞机制。
Cells migrating through physiologically relevant three-dimensional (3D) substrates such as cell-derived matrix (CDM) use actomyosin and vimentin intermediate filaments to pull the nucleus forward and pressurize the front of the cell as part of the nuclear piston mechanism of 3D migration. In this study, we tested the role of the cytoskeleton cross-linking protein plectin in facilitating the movement of the nucleus through 3D matrices. We find that the interaction of F-actin and vimentin filaments in cells on 2D glass and in 3D CDM requires actomyosin contractility. Plectin also facilitated these interactions and interacts with vimentin in response to NMII contractility and substrate stiffness, suggesting that the association of plectin and vimentin is mechanosensitive. We find that this mechanosensitive plectin complex slows down 2D migration but is critical for pulling the nucleus forward and generating compartmentalized intracellular pressure in 3D CDM, as well as low-pressure lamellipodial migration in 3D collagen. Finally, plectin expression helped to polarize NMII to in front of the nucleus and to localize the vimentin network around the nucleus. Together, our data suggest that plectin cross-links vimentin and actomyosin filaments, organizes the vimentin network, and polarizes NMII to facilitate the nuclear piston mechanism of 3D cell migration.