2016年11月12日
The C-terminal region of Reelin is necessary for proper positioning of a subset of Purkinje cells in the postnatal cerebellum.
Neuroscience
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- 巻
- 336
- 号
- 開始ページ
- 20
- 終了ページ
- 29
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.neuroscience.2016.08.039
- 出版者・発行元
- PERGAMON-ELSEVIER SCIENCE LTD
In the normal cerebellum, Purkinje cells (PCs) are generated in a zone along the ventricular surface, migrate radially, and align to form a single-cell layer. However, in mice lacking the secreted protein Reelin or its downstream adaptor protein Dab1, the majority of PCs are located ectopically in the deep cerebellar mass. Nonetheless, how Reelin regulates migration and alignment of PCs remains incompletely understood. Reelin has a highly-conserved C-terminal region (CTR), which is required for its full activity. Here, we report an abnormality of the cerebellum in Reelin CTR-lacking knock-in (ΔC-KI) mice. In the ΔC-KI mice, cerebellar formation was largely normal, but some PCs in selected regions were found to be located ectopically and to frequently form clusters. Ectopic PCs contained a higher amount of Dab1 protein and functional Reelin receptors, including mainly very low-density lipoprotein receptor than correctly-aligned PCs. Decreasing Dab1 gene dosage exacerbated mislocalization of PCs and the cerebellar structure in Reelin ΔC-KI mice. These results indicate that ectopic PCs in ΔC-KI mice failed to receive sufficient Reelin signaling en route to their final destinations. Further, we also found that Reelin protein with intact CTR binds preferentially to PCs. Thus, it was suggested that the extent or quality of Reelin/Dab1 signaling that PCs require for correct positioning vary and that Reelin with intact CTR is required for that of a certain subset of PCs.
- リンク情報
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- DOI
- https://doi.org/10.1016/j.neuroscience.2016.08.039
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201702207035385744
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/27586054
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000385900800003&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1016/j.neuroscience.2016.08.039
- ISSN : 0306-4522
- eISSN : 1873-7544
- J-Global ID : 201702207035385744
- PubMed ID : 27586054
- Web of Science ID : WOS:000385900800003