NMII forms a contractile transcellular sarcomeric network to regulate apical cell junctions and tissue geometry.

NMII forms a contractile transcellular sarcomeric network to regulate apical cell junctions and tissue geometry.
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DOI:
10.1016/j.cub.2013.03.039
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发表时间:
2013-04-22
期刊:
影响因子:
9.2
通讯作者:
Kachar, Bechara
Kachar, Bechara
中科院分区:
生物学1区
文献类型:
--
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

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非肌肉肌球蛋白II(NMII)被认为是上皮顶端连接内力的主要整合者,介导上皮组织形态发生和张力稳态。由于细胞-细胞粘附失败,匪II中的突变与许多疾病相关。然而,NMII产生和响应沿着细胞间连接线的张力的组织和精确机制仍然未知。我们发现,双极NMII纤维的周期性组装体与连接周肌动蛋白和α-辅肌动蛋白交织在一起,在每个上皮细胞周围形成连续的肌样肌节单位带(约400 - 600 nm)。值得注意的是,相邻细胞的肌节在连接线上精确配对,形成一个完整的跨细胞收缩网络。成对的肌节的收缩/松弛同时影响顶端细胞形状和组织几何形状的变化。我们显示了NMII异构体在异型连接处的差异分布和异构体之间补偿的证据。我们的研究结果提供了一个模型,如何NMII力的产生是影响沿着交界处周边的每个细胞,并在上皮组织中的相邻细胞之间的沟通。肌节网络还提供了一个明确的目标,以调查的多种作用,NMII的交界处的稳态,以及在发展和疾病。
Nonmuscle myosin II (NMII) is thought to be the master integrator of force within epithelial apical junctions, mediating epithelial tissue morphogenesis and tensional homeostasis. Mutations in NMII are associated with a number of diseases due to failures in cell-cell adhesion. However, the organization and the precise mechanism by which NMII generates and responds to tension along the intercellular junctional line are still not known. We discovered that periodic assemblies of bipolar NMII filaments interlace with perijunctional actin and α-actinin to form a continuous belt of muscle-like sarcomeric units (~400 – 600 nm) around each epithelial cell. Remarkably, the sarcomeres of adjacent cells are precisely paired across the junctional line forming an integrated, transcellular contractile network. The contraction/relaxation of paired sarcomeres concomitantly impacts changes in apical cell shape and tissue geometry. We show differential distribution of NMII isoforms across heterotypic junctions and evidence for compensation between isoforms. Our results provide a model for how NMII force generation is effected along the junctional perimeter of each cell, and communicated across neighboring cells in the epithelial organization. The sarcomeric network also provides a well-defined target to investigate the multiple roles of NMII in junctional homeostasis as well as in development and disease.
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