Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation

Ken ichi Dewa, Nariko Arimura, Wataru Kakegawa, Masayuki Itoh, Toma Adachi, Satoshi Miyashita, Yukiko U. Inoue, Kento Hizawa, Kei Hori, Natsumi Honjoya, Haruya Yagishita, Shinichiro Taya, Taisuke Miyazaki, Chika Usui, Shoji Tatsumoto, Akiko Tsuzuki, Hirotomo Uetake, Kazuhisa Sakai, Kazuhiro Yamakawa, Takuya SasakiJun Nagai, Yoshiya Kawaguchi, Masaki Sone, Takayoshi Inoue, Yasuhiro Go, Noritaka Ichinohe, Kozo Kaibuchi, Masahiko Watanabe, Schuichi Koizumi, Michisuke Yuzaki, Mikio Hoshino

Research output: Contribution to journalArticlepeer-review

Abstract

In the central nervous system, astrocytes enable appropriate synapse function through glutamate clearance from the synaptic cleft; however, it remains unclear how astrocytic glutamate transporters function at peri-synaptic contact. Here, we report that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synapse formation and function in the developing cerebellum. Dscam-mutant mice show defects in CF synapse translocation as is observed in loss of function mutations in the astrocytic glutamate transporter GLAST expressed in Bergmann glia. These mice show impaired glutamate clearance and the delocalization of GLAST away from the cleft of parallel fibre (PF) synapse. GLAST complexes with the extracellular domain of DSCAM. Riluzole, as an activator of GLAST-mediated uptake, rescues the proximal impairment in CF synapse formation in Purkinje cell-selective Dscam-deficient mice. DSCAM is required for motor learning, but not gross motor coordination. In conclusion, the intercellular association of synaptic and astrocyte proteins is important for synapse formation and function in neural transmission.

Original languageEnglish
Article number458
JournalNature communications
Volume15
Issue number1
DOIs
Publication statusPublished - 12-2024

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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