Vinculin is required for neuronal mechanosensing but not for axon outgrowth.
Vinculin is required for neuronal mechanosensing but not for axon outgrowth.
复制标题
纽蛋白是神经元机械传感所必需的，但不是轴突生长所必需的。
DOI：
10.1016/j.yexcr.2021.112805
复制
发表时间：
2021
影响因子：
3.7
通讯作者：
Wang DY
中科院分区：
文献类型：
--
作者：
Wang DY
整合素受体是与细胞外基质（ECM）结合的跨膜蛋白。在大多数动物细胞类型中，整联蛋白在粘着斑处与接头蛋白聚集在一起，所述接头蛋白感知并响应外部机械信号。在中枢神经系统（CNS）中，ECM蛋白分布稀疏，组织相对柔软，神经元不形成局灶性粘连。因此，神经元如何感知组织硬度目前还知之甚少。在这里，我们发现，整合素和整合素相关蛋白塔林和黏着斑激酶（FAK）所需的神经过程的生长。然而，神经纤维素，而不是所需的神经突生长是一个关键的调节器的整合素介导的机械神经元。在生长过程中，CNS衍生细胞的轴突的生长锥对其环境施加约10-12 Pa的动态应力，并且轴突在软（0.4 kPa）基质上比在硬（8 kPa）基质上生长得显著更长。黏着斑蛋白的耗尽阻断了生长锥区分软质和硬质基质的能力。这些数据表明，黏着斑蛋白在神经元作为一个关键的机械传感器，参与调节生长锥运动。
Integrin receptors are transmembrane proteins that bind to the extracellular matrix (ECM). In most animal cell types integrins cluster together with adaptor proteins at focal adhesions that sense and respond to external mechanical signals. In the central nervous system (CNS), ECM proteins are sparsely distributed, the tissue is comparatively soft and neurons do not form focal adhesions. Thus, how neurons sense tissue stiffness is currently poorly understood. Here, we found that integrins and the integrin-associated proteins talin and focal adhesion kinase (FAK) are required for the outgrowth of neuronal processes. Vinculin, however, whilst not required for neurite outgrowth was a key regulator of integrin-mediated mechanosensing of neurons. During growth, growth cones of axons of CNS derived cells exerted dynamic stresses of around 10–12 Pa on their environment, and axons grew significantly longer on soft (0.4 kPa) compared to stiff (8 kPa) substrates. Depletion of vinculin blocked this ability of growth cones to distinguish between soft and stiff substrates. These data suggest that vinculin in neurons acts as a key mechanosensor, involved in the regulation of growth cone motility.
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