文章基本信息

标题：ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function
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作者：Takashi Sugiyama ; Naoya Murao ; Hisae Kadowaki 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：7
页码：1-24
DOI：10.1016/j.isci.2021.102758
语种：English
出版社：Elsevier
摘要：SummaryDerlin 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 ofDerlin-1orDerlin-2in 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 outgrowthin vitroandin vivoand 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.Graphical abstractDisplay OmittedHighlights•Derlin-1 and Derlin-2 are essential for postnatal brain development and function•Chemical chaperon does not ameliorate the phenotype of Derlin-deficient neuron•Derlin regulates SREBP-2 activation and promotes brain cholesterol biosynthesis•Derlin-mediated cholesterol biosynthesis is essential for neurite outgrowthBiological sciences; Neuroscience; Molecular neuroscience