TY - JOUR
T1 - Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation
AU - Dewa, Ken ichi
AU - Arimura, Nariko
AU - Kakegawa, Wataru
AU - Itoh, Masayuki
AU - Adachi, Toma
AU - Miyashita, Satoshi
AU - Inoue, Yukiko U.
AU - Hizawa, Kento
AU - Hori, Kei
AU - Honjoya, Natsumi
AU - Yagishita, Haruya
AU - Taya, Shinichiro
AU - Miyazaki, Taisuke
AU - Usui, Chika
AU - Tatsumoto, Shoji
AU - Tsuzuki, Akiko
AU - Uetake, Hirotomo
AU - Sakai, Kazuhisa
AU - Yamakawa, Kazuhiro
AU - Sasaki, Takuya
AU - Nagai, Jun
AU - Kawaguchi, Yoshiya
AU - Sone, Masaki
AU - Inoue, Takayoshi
AU - Go, Yasuhiro
AU - Ichinohe, Noritaka
AU - Kaibuchi, Kozo
AU - Watanabe, Masahiko
AU - Koizumi, Schuichi
AU - Yuzaki, Michisuke
AU - Hoshino, Mikio
N1 - Publisher Copyright:
© 2024, The Author(s).
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-44579-z
DO - 10.1038/s41467-023-44579-z
M3 - Article
C2 - 38302444
AN - SCOPUS:85183684280
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 458
ER -