| Title: |
ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function |
| Authors: |
Takashi Sugiyama, Naoya Murao, Hisae Kadowaki, Keizo Takao, Tsuyoshi Miyakawa, Yosuke Matsushita, Toyomasa Katagiri, Akira Futatsugi, Yohei Shinmyo, Hiroshi Kawasaki, Juro Sakai, Kazutaka Shiomi, Masamitsu Nakazato, Kohsuke Takeda, Katsuhiko Mikoshiba, Hidde L. Ploegh, Hidenori Ichijo, Hideki Nishitoh |
| Source: |
iScience, Vol 24, Iss 7, Pp 102758- (2021) |
| Publisher Information: |
Elsevier, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Science |
| Subject Terms: |
Biological sciences, Neuroscience, Molecular neuroscience, Science |
| More Details: |
Summary: Derlin family members (Derlins) are primarily known as components of the endoplasmic reticulum-associated degradation pathway that eliminates misfolded proteins. Here we report a function of Derlins in the brain development. Deletion of Derlin-1 or Derlin-2 in the central nervous system of mice impaired postnatal brain development, particularly of the cerebellum and striatum, and induced motor control deficits. Derlin-1 or Derlin-2 deficiency reduced neurite outgrowth in vitro and in vivo and surprisingly also inhibited sterol regulatory element binding protein 2 (SREBP-2)-mediated brain cholesterol biosynthesis. In addition, reduced neurite outgrowth due to Derlin-1 deficiency was rescued by SREBP-2 pathway activation. Overall, our findings demonstrate that Derlins sustain brain cholesterol biosynthesis, which is essential for appropriate postnatal brain development and function. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2589-0042 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2589004221007264; https://doaj.org/toc/2589-0042 |
| DOI: |
10.1016/j.isci.2021.102758 |
| Access URL: |
https://doaj.org/article/b69667e8cdc0451bb9c8130fc2b00445 |
| Accession Number: |
edsdoj.b69667e8cdc0451bb9c8130fc2b00445 |
| Database: |
Directory of Open Access Journals |
