Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation
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Published:2024-02-01
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Dewa Ken-ichi, Arimura NarikoORCID, Kakegawa Wataru, Itoh Masayuki, Adachi Toma, Miyashita Satoshi, Inoue Yukiko U.ORCID, Hizawa Kento, Hori Kei, Honjoya Natsumi, Yagishita Haruya, Taya Shinichiro, Miyazaki Taisuke, Usui Chika, Tatsumoto Shoji, Tsuzuki Akiko, Uetake Hirotomo, Sakai Kazuhisa, Yamakawa Kazuhiro, Sasaki TakuyaORCID, Nagai JunORCID, Kawaguchi YoshiyaORCID, Sone MasakiORCID, Inoue TakayoshiORCID, Go YasuhiroORCID, Ichinohe Noritaka, Kaibuchi Kozo, Watanabe Masahiko, Koizumi SchuichiORCID, Yuzaki MichisukeORCID, Hoshino MikioORCID
Abstract
AbstractIn 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.
Funder
Naito Foundation Japan Agency for Medical Research and Development MEXT | Japan Society for the Promotion of Science Daiichi Sankyo Foundation of Life Science MEXT | JST | Core Research for Evolutional Science and Technology
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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