Molecular pathogenesis of neurological diseases caused by disruption of early Golgi quality control system
Description: Rer1 is a retrieval receptor for endoplasmic reticulum (ER) retention of various ER membrane proteins and unassembled or immature components of membrane protein complexes. 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. 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.
Amount: ¥4,940,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2017-04-01
End date: 2021-03-31
Investigator: Taichi Hara
Institution: Waseda University
Funded outputs count: 4
Funder award ID: 17K08621
OpenAlex ID: G547282071