Rer1-mediated quality control system is required for neural stem cell maintenance during cerebral cortex development

Taichi Hara, Ikuko Maejima, Tomoko Akuzawa, Rika Hirai, Hisae Kobayashi, Satoshi Tsukamoto, Mika Tsunoda, Aguri Ono, Shota Yamakoshi, Satoshi Oikawa, Ken Sato

研究成果: Article

2 被引用数 (Scopus)

抄録

Rer1 is a retrieval receptor for endoplasmic reticulum (ER) retention of various ER membrane proteins and unassembled or immature components of membrane protein complexes. However, its physiological functions during mammalian development remain unclear. This study aimed to investigate the role of Rer1-mediated quality control system in mammalian development. We show that Rer1 is required for the sufficient cell surface expression and activity of γ-secretase complex, which modulates Notch signaling during mouse cerebral cortex development. When Rer1 was depleted in the mouse cerebral cortex, the number of neural stem cells decreased significantly, and malformation of the cerebral cortex was observed. Rer1 loss reduced γ-secretase activity and downregulated Notch signaling in the developing cerebral cortex. In Rer1-deficient cells, a subpopulation of γ-secretase complexes and components was transported to and degraded in lysosomes, thereby significantly reducing the amount of γ-secretase complex on the cell surface. These results suggest that Rer1 maintains Notch signaling by maintaining sufficient expression of the γ-secretase complex on the cell surface and regulating neural stem cell maintenance during cerebral cortex development.

本文言語English
論文番号e1007647
ジャーナルPLoS Genetics
14
9
DOI
出版ステータスPublished - 2018 9

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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