Journal Article

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

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

2024

Overview

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. The glutamate transporter GLAST in astrocyte regulates synapse function by glutamate clearance. Here, the authors show that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synaptogenesis through the intercellular association with GLAST in the developing cerebellum.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/1 / 13/109 / 14/19 / 14/28 / 14/35 / 38/88 / 38/91 / 631/378/2571 / 631/378/2571/2577 / 631/378/2596/1308 / 64/60 / 9/74 / Adhesion / Astrocytes / Cell adhesion / Cell adhesion & migration / Cell adhesion molecules / Central nervous system / Cerebellum / Clearances / Down syndrome / Down's syndrome / DSCAM protein / Glutamic acid transporter / Humanities and Social Sciences / Localization / Motor skill learning / multidisciplinary / Neural cell adhesion molecule / Neuronal-glial interactions / Purkinje cells / Science / Science (multidisciplinary) / Synapses / Synaptic cleft / Synaptogenesis / Translocation