Hyaluronan synthesis supports glutamate transporter activity

Mariko Kato Hayashi, Tomoki Nishioka, Hideo Shimizu, Kanako Takahashi, Wataru Kakegawa, Tetsuri Mikami, Yuri Hirayama, Schuichi Koizumi, Sachiko Yoshida, Michisuke Yuzaki, Markku Tammi, Yuko Sekino, Kozo Kaibuchi, Yukari Shigemoto-Mogami, Masato Yasui, Kaoru Sato

Research output: Contribution to journalArticle

Abstract

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. (Figure presented.). Cover Image for this issue: doi: 10.1111/jnc.14516.

Original languageEnglish
Pages (from-to)249-263
Number of pages15
JournalJournal of Neurochemistry
Volume150
Issue number3
DOIs
Publication statusPublished - 2019 Aug

Keywords

  • excitotoxicity
  • glutamate transporter
  • hyaluronan
  • hyaluronan synthase
  • perineuronal nets

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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  • Cite this

    Hayashi, M. K., 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. (2019). Hyaluronan synthesis supports glutamate transporter activity. Journal of Neurochemistry, 150(3), 249-263. https://doi.org/10.1111/jnc.14791