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Hyaluronan synthesis supports glutamate transporter activity
Author(s) -
Hayashi Mariko Kato,
Nishioka Tomoki,
Shimizu Hideo,
Takahashi Kanako,
Kakegawa Wataru,
Mikami Tetsuri,
Hirayama Yuri,
Koizumi Schuichi,
Yoshida Sachiko,
Yuzaki Michisuke,
Tammi Markku,
Sekino Yuko,
Kaibuchi Kozo,
ShigemotoMogami Yukari,
Yasui Masato,
Sato Kaoru
Publication year - 2019
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14791
Subject(s) - excitotoxicity , glutamate receptor , excitatory postsynaptic potential , microbiology and biotechnology , neuroscience , neurotransmission , perineuronal net , chemistry , glutamatergic , transporter , biochemistry , biology , central nervous system , inhibitory postsynaptic potential , receptor , gene
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 .