Nature Communications (Feb 2024)
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,
- Mikio Hoshino
Affiliations
- Ken-ichi Dewa
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Nariko Arimura
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Wataru Kakegawa
- Department of Physiology, Keio University School of Medicine
- Masayuki Itoh
- Department of Physiology, Keio University School of Medicine
- Toma Adachi
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Satoshi Miyashita
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Yukiko U. Inoue
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Kento Hizawa
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
- Kei Hori
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Natsumi Honjoya
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
- Haruya Yagishita
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
- Shinichiro Taya
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Taisuke Miyazaki
- Department of Health Sciences, School of Medicine, Hokkaido University
- Chika Usui
- Cognitive Genomics Research Group, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
- Shoji Tatsumoto
- Cognitive Genomics Research Group, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
- Akiko Tsuzuki
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Hirotomo Uetake
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Kazuhisa Sakai
- Department of Ultrastructural Research, National Institute of Neuroscience, NCNP
- Kazuhiro Yamakawa
- Department of Neurodevelopmental Disorder Genetics, Nagoya City University Graduate School of Medicine
- Takuya Sasaki
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
- Jun Nagai
- Laboratory for Glia-Neuron Circuit Dynamics, RIKEN Center for Brain Science
- Yoshiya Kawaguchi
- Department of Life Science Frontiers, Center for iPS cell Research and Application (CiRA), Kyoto University
- Masaki Sone
- Department of Biomolecular Science, Faculty of Science, Toho University
- Takayoshi Inoue
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- Yasuhiro Go
- Cognitive Genomics Research Group, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences
- Noritaka Ichinohe
- Department of Ultrastructural Research, National Institute of Neuroscience, NCNP
- Kozo Kaibuchi
- Division of Cell Biology, International Center for Brain Science, Fujita Health University
- Masahiko Watanabe
- Department of Anatomy, Faculty of Medicine, Hokkaido University
- Schuichi Koizumi
- Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo
- Michisuke Yuzaki
- Department of Physiology, Keio University School of Medicine
- Mikio Hoshino
- Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP
- DOI
- https://doi.org/10.1038/s41467-023-44579-z
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
