@article{42b2f8655a3040b08eef2bdf7cc0958d,
title = "Rer1-mediated quality control system is required for neural stem cell maintenance during cerebral cortex development",
abstract = "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.",
author = "Taichi Hara and Ikuko Maejima and Tomoko Akuzawa and Rika Hirai and Hisae Kobayashi and Satoshi Tsukamoto and Mika Tsunoda and Aguri Ono and Shota Yamakoshi and Satoshi Oikawa and Ken Sato",
note = "Funding Information: TH was supported by research grants from the Takeda Science Foundation(http://www.takeda-sci.or.jp/), the Nakajima Foundation(http://www.nakajimafound.or.jp/), the Astellas Foundation for Research on Metabolic Disorders(https://www.astellas.com/jp/byoutai/), and MEXT JSPS KAKENHI (Grant Number:17K08621(https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K08621), 15K19002 (https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15K19002/),24116702 (https://kaken.nii.ac.jp/grant/KAKENHI-PUBLICLY-24116702/), and 24590341(https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24590341/). This research is also supported by the research program for conquering intractable disease from Japan Agency for Medical Research and Development, AMED(Grant Number 26310301, http://www.amed.go.jp/en/) and is a part pf the outcome of research performed under a Waseda University Grant for Special Research Project (Project number: 2017S-142 and 2018K-349). KS was supported by the JSPS KAKENHI (Grant Number: 17K19377, 17H03669), the Uehara Memorial Foundation, and Takeda Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Drs. Toshio Kitamura (University of Tokyo) and Tohru Ishitani for providing biological reagents. We thank Drs. Hideaki Miwa and Yuchio Yanagawa (Gunma University) for their suggestions on the mouse behavioral analysis. We thank Aya Matsui, Masataka Shimizu, and Yasuhiro Makita (Waseda University) for assistance in data analysis. We also thank Dr. Takeshi Kawauchi (Institute of Biomedical Research and Innovation) for his valuable advice. We thank Dr. Nobukatsu Morooka and other members of the Sato laboratory for their technical assistance and discussions. We thank Mayumi Seto for helping preparation of manuscript. Publisher Copyright: {\textcopyright} 2018 Hara et al. http://creativecommons.org/licenses/by/4.0/.",
year = "2018",
month = sep,
doi = "10.1371/journal.pgen.1007647",
language = "English",
volume = "14",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "9",
}