| First Author | Sugiyama T | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 7 | Pages | 102758 |
| PubMed ID | 34355142 | Mgi Jnum | J:311891 |
| Mgi Id | MGI:6780799 | Doi | 10.1016/j.isci.2021.102758 |
| Citation | Sugiyama T, et al. (2021) ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function. iScience 24(7):102758 |
| abstractText | 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. |
