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CDC42EP4, a perisynaptic scaffold protein in Bergmann glia, is required for glutamatergic tripartite synapse configuration
http://hdl.handle.net/2237/00029248
http://hdl.handle.net/2237/000292485c805ef0-9046-4fb0-96cb-0ae459debe3f
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
NCI2018 (1.9 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2019-02-06 | |||||
| タイトル | ||||||
| タイトル | CDC42EP4, a perisynaptic scaffold protein in Bergmann glia, is required for glutamatergic tripartite synapse configuration | |||||
| 言語 | en | |||||
| 著者 |
Ageta-Ishihara, Natsumi
× Ageta-Ishihara, Natsumi× Konno, Kohtarou× Yamazaki, Maya× Abe, Manabu× Sakimura, Kenji× Watanabe, Masahiko× Kinoshita, Makoto |
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| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Tripartite synapse | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Bergmann glia | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Purkinje cells | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | MYH10/nonmuscle myosin IIB | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Septin | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Synaptic contact | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Configuration of tripartite synapses, comprising the pre-, post-, and peri-synaptic components (axon terminal or bouton, dendritic spine, and astroglial terminal process), is a critical determinant of neurotransmitter kinetics and hence synaptic transmission. However, little is known about molecular basis for the regulation of tripartite synapse morphology. Previous studies showed that CDC42EP4, an effector protein of a cell morphogenesis regulator CDC42, is expressed exclusively in Bergmann glia in the cerebellar cortex, that it forms tight complex with the septin heterooligomer, and that it interacts indirectly with the glutamate transporter GLAST and MYH10/nonmuscle myosin ΙΙB. Scrutiny of Cdc42ep4−/− mice had revealed that the CDC42EP4-septins-GLAST interaction facilitates glutamate clearance, while the role for CDC42EP4-septins-MYH10 interaction has remained unsolved. Here, we find anomalous configuration of the tripartite synapses comprising the parallel fiber boutons, dendritic spines of Purkinje cells, and Bergmann glial processes in Cdc42ep4^−/− mice. The complex anomalies include 1) recession of Bergmann glial membranes from the nearest active zones, and 2) extension of nonactive synaptic contact around active zone. In line with the recession of Bergmann glial membranes by the loss of CDC42EP4, overexpression of CDC42EP4 in heterologous cells promotes cell spreading and partitioning of MYH10 to insoluble (i.e., active) fraction. Paradoxically, however, Cdc42ep4^−/− cerebellum contained significantly more MYH10 and N-cadherin, which is attributed to secondary neuronal response mainly in Purkinje cells. Given cooperative actions of N-cadherin and MYH10 for adhesion between neurons, we speculate that their augmentation may reflect the extension of nonactive synaptic contacts in Cdc42ep4^−/− cerebellum. Transcellular mechanism that links the absence of CDC42EP4 in Bergmann glia to the augmentation of N-cadherin and MYH10 in neurons is currently unknown, but the phenotypic similarity to GLAST-null mice indicates involvement of the glutamate intolerance. Together, the unique phenotype of Cdc42ep4^−/− mice provides a clue to novel molecular network underlying tripartite synapse configuration. | |||||
| 言語 | en | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | ファイル公開：2019-10-01 | |||||
| 言語 | ja | |||||
| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 出版タイプ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.neuint.2018.01.003 | |||||
| ISSN（print） | ||||||
| 収録物識別子タイプ | PISSN | |||||
| 収録物識別子 | 0197-0186 | |||||
| 書誌情報 |
en : Neurochemistry International 巻 119, p. 190-198, 発行日 2018-10 |
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| 著者版フラグ | ||||||
| 値 | author | |||||
