Tau modulates Schwann cell proliferation, migration and differentiation following peripheral nerve injury
Tau modulates Schwann cell proliferation, migration and differentiation following peripheral nerve injury
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Tau 调节周围神经损伤后雪旺细胞的增殖、迁移和分化
DOI：
10.1242/jcs.222059
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发表时间：
2019-03-01
影响因子：
4
通讯作者：
Li, Shiying
中科院分区：
文献类型：
--
作者：
Yi, Sheng;Liu, Qianyan;Li, Shiying
Tau蛋白（由基因微管相关蛋白Tau， Mapt编码）对微管的组装和稳定以及神经系统的功能维持至关重要。Tau蛋白在神经元中非常丰富，在星形胶质细胞和少突胶质细胞中也可以检测到。然而，尚不清楚tau蛋白是否存在于雪旺细胞中，雪旺细胞是周围神经系统中独特的胶质细胞。在这里，我们研究了tau及其编码mRNA的存在。在培养的雪旺细胞中发现tau蛋白存在于这些细胞中。Mapt基因沉默可促进雪旺细胞增殖，抑制雪旺细胞的迁移和分化。在体内应用Mapt siRNA抑制坐骨神经损伤后雪旺细胞的迁移。与此一致的是，mapt敲除小鼠的雪旺细胞增殖增加，迁移减少。注射Mapt siRNA的大鼠和Mapt敲除小鼠也表现出髓鞘和脂质碎片清除受损。细胞骨架蛋白α -微管蛋白和f -肌动蛋白的表达和分布也被破坏。这些发现证明了tau蛋白在雪旺细胞中的存在及其生物学作用，并扩大了我们对tau蛋白在神经系统中的功能的认识。
Tau protein (encoded by the gene microtubule-associated protein tau, Mapt) is essential for the assembly and stability of microtubule and the functional maintenance of the nervous system. Tau is highly abundant in neurons and is detectable in astrocytes and oligodendrocytes. However, whether tau is present in Schwann cells, the unique glial cells in the peripheral nervous system, is unclear. Here, we investigated the presence of tau and its coding mRNA. Mapt, in cultured Schwann cells and find that tau is present in these cells. Gene silencing of Mapt promoted Schwann cell proliferation and inhibited Schwann cell migration and differentiation. In vivo application of Mapt siRNA suppressed the migration of Schwann cells after sciatic nerve injury. Consistent with this, Mapt-knockout mice showed elevated proliferation and reduced migration of Schwann cells. Rats injected with Mapt siRNA and Mapt-knockout mice also exhibited impaired myelin and lipid debris clearance. The expression and distribution of the cytoskeleton proteins alpha-tubulin and F-actin were also disrupted in these animals. These findings demonstrate the existence and biological effects of tau in Schwann cells, and expand our understanding of the function of tau in the nervous system.