Bulgakova Natalia A, Wellmann Jutta, Brown Nicholas H
Department of Physiology, Development and Neuroscience and The Gurdon Institute, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Department of Physiology, Development and Neuroscience and The Gurdon Institute, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK
Open Biol. 2017 Apr;7(4). doi: 10.1098/rsob.160250.
Cells in an organism are subjected to numerous sources of external and internal forces, and are able to sense and respond to these forces. Integrin-mediated adhesion links the extracellular matrix outside cells to the cytoskeleton inside, and participates in sensing, transmitting and responding to forces. While integrin adhesion rapidly adapts to changes in forces in isolated migrating cells, it is not known whether similar or more complex responses occur within intact, developing tissues. Here, we studied changes in integrin adhesion composition upon different contractility conditions in embryonic muscles. We discovered that all integrin adhesion components tested were still present at muscle attachment sites (MASs) when either cytoplasmic or muscle myosin II was genetically removed, suggesting a primary role of a developmental programme in the initial assembly of integrin adhesions. Contractility does, however, increase the levels of integrin adhesion components, suggesting a mechanism to balance the strength of muscle attachment to the force of muscle contraction. Perturbing contractility in distinct ways, by genetic removal of either cytoplasmic or muscle myosin II or eliminating muscle innervation, each caused unique alterations to the stoichiometry at MASs. This suggests that different integrin-associated proteins are added to counteract different kinds of force increase.
生物体中的细胞会受到多种外部和内部力量的作用，并且能够感知并对这些力量做出反应。整合素介导的黏附将细胞外的细胞外基质与细胞内的细胞骨架连接起来，并参与力的感知、传递和响应。虽然整合素黏附在分离的迁移细胞中能迅速适应力的变化，但在完整的发育组织中是否会发生类似或更复杂的反应尚不清楚。在这里，我们研究了胚胎肌肉在不同收缩条件下整合素黏附成分的变化。我们发现，当通过基因手段去除细胞质或肌肉肌球蛋白II时，所有测试的整合素黏附成分仍存在于肌肉附着位点（MASs），这表明发育程序在整合素黏附的初始组装中起主要作用。然而，收缩性确实会增加整合素黏附成分的水平，这表明存在一种机制来平衡肌肉附着强度与肌肉收缩力。通过基因去除细胞质或肌肉肌球蛋白II或消除肌肉神经支配等不同方式扰乱收缩性，每种方式都会导致MASs处化学计量比发生独特变化。这表明添加了不同的整合素相关蛋白以抵消不同类型的力增加。
