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.
Highlights
Synthesized proteins are primarily assessed by the endoplasmic reticulum (ER) quality control system for correct folding, modification, and complex formation
We showed that Rer1 functions as an early-Golgi quality control pathway that maintains γ-secretase activity by maintaining sufficient cell surface expression of γ-secretase complex during cerebral cortex development, thereby modulating Notch signaling
Rer1trap/trap mice were embryonic lethal, as reported previously [22], indicating that Rer1 plays an essential role in mouse early development (S1D Fig)
Summary
Synthesized proteins are primarily assessed by the ER quality control system for correct folding, modification, and complex formation. Some immature or misfolded proteins escape from the ER to post-ER compartments. Rer1-mediated quality control system in cerebral cortex development. 17K08621), 15K19002 (https://kaken.nii.ac.jp/ grant/KAKENHI-PROJECT-15K19002/),24116702 (https://kaken.nii.ac.jp/grant/KAKENHI-PUBLICLY24116702/), and 24590341(https://kaken.nii.ac.jp/ grant/KAKENHI-PROJECT-24590341/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
