ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function
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
Abstract
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.
Topics & Concepts
Motor functionBrain functionFunction (biology)Brain developmentNeuroscienceEndoplasmic-reticulum-associated protein degradationCell biologyBiologyChemistryBioinformaticsMedicinePhysical medicine and rehabilitationUnfolded protein responseEndoplasmic reticulumEndoplasmic Reticulum Stress and DiseaseAdipose Tissue and MetabolismRNA regulation and disease