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 Sasaki, Jun Nagai, Yoshiya Kawaguchi, Masaki Sone, Takayoshi Inoue, Yasuhiro Go, Noritaka Ichinohe, Kozo Kaibuchi, Masahiko Watanabe, Schuichi Koizumi, Michisuke Yuzaki and Mikio Hoshino ()
Additional contact information
Ken-ichi Dewa: National Institute of Neuroscience, NCNP
Nariko Arimura: National Institute of Neuroscience, NCNP
Wataru Kakegawa: Keio University School of Medicine
Masayuki Itoh: Keio University School of Medicine
Toma Adachi: National Institute of Neuroscience, NCNP
Satoshi Miyashita: National Institute of Neuroscience, NCNP
Yukiko U. Inoue: National Institute of Neuroscience, NCNP
Kento Hizawa: Graduate School of Pharmaceutical Sciences, Tohoku University
Kei Hori: National Institute of Neuroscience, NCNP
Natsumi Honjoya: Graduate School of Pharmaceutical Sciences, Tohoku University
Haruya Yagishita: Graduate School of Pharmaceutical Sciences, Tohoku University
Shinichiro Taya: National Institute of Neuroscience, NCNP
Taisuke Miyazaki: School of Medicine, Hokkaido University
Chika Usui: Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
Shoji Tatsumoto: Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
Akiko Tsuzuki: National Institute of Neuroscience, NCNP
Hirotomo Uetake: National Institute of Neuroscience, NCNP
Kazuhisa Sakai: National Institute of Neuroscience, NCNP
Kazuhiro Yamakawa: Nagoya City University Graduate School of Medicine
Takuya Sasaki: Graduate School of Pharmaceutical Sciences, Tohoku University
Jun Nagai: RIKEN Center for Brain Science
Yoshiya Kawaguchi: Center for iPS cell Research and Application (CiRA), Kyoto University
Masaki Sone: Faculty of Science, Toho University
Takayoshi Inoue: National Institute of Neuroscience, NCNP
Yasuhiro Go: Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
Noritaka Ichinohe: National Institute of Neuroscience, NCNP
Kozo Kaibuchi: International Center for Brain Science, Fujita Health University
Masahiko Watanabe: Faculty of Medicine, Hokkaido University
Schuichi Koizumi: Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo
Michisuke Yuzaki: Keio University School of Medicine
Mikio Hoshino: National Institute of Neuroscience, NCNP

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-023-44579-z

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