ハヤシ マリコ    Hayashi Mariko
   林 真理子
   所属
食健康科学部 管理栄養学科
 
生活機構研究科 生活科学研究専攻
 
女性健康科学研究所 所属教員
   職種
准教授
言語種別 英語
発行・発表の年月 2019/08
形態種別 学術雑誌
査読 査読あり
標題 Hyaluronan synthesis supports glutamate transporter activity.
執筆形態 共著
掲載誌名 J Neurochem
掲載区分国外
巻・号・頁 150(3),pp.249-263
著者・共著者 ◎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.
概要 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.
researchmap用URL https://onlinelibrary.wiley.com/doi/10.1111/jnc.14791