E-cadherin and LGN align epithelial cell divisions with tissue tension independently of cell shape
E-cadherin and LGN align epithelial cell divisions with tissue tension independently of cell shape
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DOI：
10.1073/pnas.1701703114
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发表时间：
2017-07-18
影响因子：
11.1
通讯作者：
Gloerich, Martijn
中科院分区：
文献类型：
--
作者：
Hart, Kevin C.;Tan, Jiongyi;Gloerich, Martijn
组织形态发生需要细胞行为的协调调节，其包括限定子细胞在组织中的位置的细胞分裂的方向。细胞分裂方向是由来自局部组织环境的生化和机械信号指示的，但是这些信号如何控制有丝分裂纺锤体方向还不完全清楚。在这里，我们测试了如何在上皮细胞单层的机械张力被感知到定向细胞分裂。整个Madin-Darby犬肾细胞单层的张力增加了一个低水平的单轴拉伸，定向细胞分裂与拉伸轴无关的方向的细胞长轴。我们证明了牵张诱导的分裂方向需要通过E-钙粘蛋白细胞-细胞粘附的机械转导。E-钙粘蛋白复合物上张力的增加促进了蛋白质LGN的交界募集，LGN是结合E-钙粘蛋白胞质尾部的纺锤体取向机制的核心成分。因此，单轴拉伸触发了LGN的极化皮质分布。选择性破坏E-钙粘蛋白的反式参与，否则粘性细胞单层，或LGN表达的损失，导致在单轴拉伸的存在下，在随机取向的细胞分裂。我们的研究结果表明，E-cadherin在感知整个组织的极化张力和将此信息转导到纺锤体取向机制以对齐细胞分裂中起着关键作用。
Tissue morphogenesis requires the coordinated regulation of cellular behavior, which includes the orientation of cell division that defines the position of daughter cells in the tissue. Cell division orientation is instructed by biochemical and mechanical signals from the local tissue environment, but how those signals control mitotic spindle orientation is not fully understood. Here, we tested how mechanical tension across an epithelial monolayer is sensed to orient cell divisions. Tension across Madin-Darby canine kidney cell monolayers was increased by a low level of uniaxial stretch, which oriented cell divisions with the stretch axis irrespective of the orientation of the cell long axis. We demonstrate that stretch-induced division orientation requiredmechanotransduction through E-cadherin cell-cell adhesions. Increased tension on the E-cadherin complex promoted the junctional recruitment of the protein LGN, a core component of the spindle orientation machinery that binds the cytosolic tail of E-cadherin. Consequently, uniaxial stretch triggered a polarized cortical distribution of LGN. Selective disruption of trans engagement of E-cadherin in an otherwise cohesive cell monolayer, or loss of LGN expression, resulted in randomly oriented cell divisions in the presence of uniaxial stretch. Our findings indicate that E-cadherin plays a key role in sensing polarized tensile forces across the tissue and transducing this information to the spindle orientation machinery to align cell divisions.