Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
Dev Cell. 2018 Jul 2;46(1):102-111.e6. doi: 10.1016/j.devcel.2018.05.031. Epub 2018 Jun 21.
Skeletal muscle cells (myofibers) are rod-shaped multinucleated cells surrounded by an extracellular matrix (ECM) basal lamina. In contrast to other cell types, nuclei in myofibers are positioned just below the plasma membrane at the cell periphery. Peripheral nuclear positioning occurs during myogenesis and is driven by myofibril crosslinking and contraction. Here we show that peripheral nuclear positioning is triggered by local accumulation of fibronectin secreted by myofibroblasts. We demonstrate that fibronectin via α5-integrin mediates peripheral nuclear positioning dependent on FAK and Src activation. Finally, we show that Cdc42, downstream of restricted fibronectin activation, is required for myofibril crosslinking but not myofibril contraction. Thus we identify that local activation of integrin by fibronectin secreted by myofibroblasts activates peripheral nuclear positioning in skeletal myofibers.
骨骼肌细胞（肌纤维）呈杆状多核细胞，被细胞外基质（ECM）基底膜包围。与其他细胞类型不同，肌纤维中的核位于细胞膜下方，位于细胞外周。核的外周定位发生在肌发生过程中，由肌原纤维交联和收缩驱动。在这里，我们表明，肌成纤维细胞分泌的纤连蛋白的局部积累触发了核的外周定位。我们证明，纤连蛋白通过α5 整联蛋白介导，依赖于 FAK 和Src 的激活，从而实现核的外周定位。最后，我们发现，受限制的纤连蛋白激活下游的 Cdc42，是肌原纤维交联所必需的，但不是肌原纤维收缩所必需的。因此，我们确定了肌成纤维细胞分泌的纤连蛋白通过整合素的局部激活，激活了骨骼肌纤维中的核的外周定位。
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