Hyaluronan synthesis supports glutamate transporter activity
Hyaluronan synthesis supports glutamate transporter activity
复制标题
透明质酸合成支持谷氨酸转运蛋白活性
DOI：
10.1111/jnc.14791
复制
发表时间：
2019
影响因子：
4.7
通讯作者：
Sato K.
中科院分区：
文献类型：
--
作者：
Hayashi MK;Nishioka T;Shimizu H;Takahashi K;Kakegawa W;Mikami T;Hirayama Y;Koizumi S;Yoshida S;Yuzaki M;Tammi M;Sekino Y;Kaibuchi K;Shigemoto-Mogami Y;Yasui M;Sato K.
透明质酸是由质膜上的透明质酸合成酶（HAS）合成、分泌和固定的，它构成了神经元体和树突周围的神经元周围网的骨干。然而，透明质酸调节中枢神经系统突触传递的分子靶点尚未完全确定。在这里，我们报道透明质酸是兴奋信号的负调节因子。在兴奋性突触，谷氨酸被谷氨酸转运体移除以关闭信号并防止兴奋性毒性。由HAS合成的透明质酸支持胶质谷氨酸转运蛋白1 （GLT1）的活性。在透明质酸酶处理和透明质酸合成抑制后，GLT1也从培养的星形胶质细胞的细胞过程中撤回。一项连续敲除研究表明，所有三种HAS亚型都将GLT1招募到细胞过程中。此外，透明质酸酶处理激活了游离大鼠海马培养的神经元，并由于兴奋毒性引起神经元损伤。我们的研究结果表明，透明质酸通过支持谷氨酸清除来帮助关闭兴奋信号。本期封面图片：doi: 10.1111/jnc.14516。
Hyaluronan is synthesized, secreted, and anchored by hyaluronan synthases (HAS) at the plasma membrane and comprises the backbone of perineuronal nets around neuronal soma and dendrites. However, the molecular targets of hyaluronan to regulate synaptic transmission in the central nervous system have not been fully identified. Here, we report that hyaluronan is a negative regulator of excitatory signals. At excitatory synapses, glutamate is removed by glutamate transporters to turn off the signal and prevent excitotoxicity. Hyaluronan synthesized by HAS supports the activity of glial glutamate transporter 1 (GLT1). GLT1 also retracted from cellular processes of cultured astrocytes after hyaluronidase treatment and hyaluronan synthesis inhibition. A serial knockout study showed that all three HAS subtypes recruit GLT1 to cellular processes. Furthermore, hyaluronidase treatment activated neurons in a dissociated rat hippocampal culture and caused neuronal damage due to excitotoxicity. Our findings reveal that hyaluronan helps to turn off excitatory signals by supporting glutamate clearance.Cover Image for this issue: doi: 10.1111/jnc.14516.