Papers

Peer-reviewed Lead author International journal
Jul, 2021

ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function

iScience
  • 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
  • Display all

Volume
24
Number
7
First page
102758
Last page
102758
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1016/j.isci.2021.102758
Publisher
Elsevier BV

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.

Link information
DOI
https://doi.org/10.1016/j.isci.2021.102758
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34355142
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324814
ID information
  • DOI : 10.1016/j.isci.2021.102758
  • ISSN : 2589-0042
  • Pubmed ID : 34355142
  • Pubmed Central ID : PMC8324814

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