Professor Taichi Hara of Waseda University’s Faculty of Human Sciences discovered that the quality control system of cell membrane proteins plays an important role in neural stem cell proliferation and maintenance in brain development. This study was done collaboratively as a team with Professor Ken Sato of Gunma University.
γ-secretase complex is a type of cell membrane protein that modulates Notch signaling, which functions to proliferate and maintain neural stem cells during when the brain is being developed. Rer1, a Golgi complex membrane protein, is known to send abnormal or immature proteins back to the endoplasmic reticulum (ER).
This study revealed that when Rer1 was deficient, a subpopulation of the γ-secretase complexes was taken to the post-ER compartments before the assembly was completed, and as a result, was transported to and degraded in the lysosome. When Rer1 was depleted in the mouse cerebral cortex, Notch signaling was downregulated due to the decrease in the amount of γ-secretase complexes in the brain, and the amount of neural stem cells decreased. The malformation of the brain and other abnormal activities were observed in such mouse revealed that the Rer1-mediated quality control system of γ-secretase complexes played a significant role in the development of the brain as well as higher brain functions.
γ-secretase complexes are involved in the generation of amyloid-β (Aβ), which is one of the causes for Alzheimer’s disease. Also, abnormality in Notch signaling, which functions in ontogenesis and maintenance of neural stem cells, is known to trigger all kinds of diseases, including neurological disorders and cancer. For these reasons, the results from this study could help better understand the onset of diseases related to γ-secretase complexes and neural stem cells and develop new treatment for them.
This study was published in PLOS Genetics on September 27, 2018.
Title: Rer1-mediated quality control system is required for neural stem cell maintenance during cerebral cortex development
Authors: Taichi Hara, Ikuko Maejima, Tomoko Akuzawa, Rika Hirai, Hisae Kobayashi, Satoshi Tsukamoto, Mika Tsunoda, Aguri Ono, Shota Yamakoshi, Satoshi Oikawa and Ken Sato
Published in: PLOS Genetics. 14(9): e1007647, DOI: 10.1371/journal.pgen.1007647
- Professor Taichi Hara
- Department of Health Science and Social Welfare, Faculty of Human Sciences, Waseda University