ID 112435
著者
Nakazawa, Takanobu The University of Tokyo|Osaka University
Hashimoto, Ryota Osaka University
Sakoori, Kazuto The University of Tokyo
Sugaya, Yuki The University of Tokyo
Tanimura, Asami The University of Tokyo
Hashimotodani, Yuki The University of Tokyo
Ohi, Kazutaka Osaka University
Yamamori, Hidenaga Osaka University
Yasuda, Yuka Osaka University
Umeda-Yano, Satomi Osaka University
Kiyama, Yuji The University of Tokyo
Konno, Kohtarou Hokkaido University
Inoue, Takeshi The University of Tokyo
Yokoyama, Kazumasa The University of Tokyo
Inoue, Takafumi Waseda University
Ohnuma, Tohru Juntendo University
Iwata, Nakao Fujita Health University
Ozaki, Norio Nagoya University
Hashimoto, Hitoshi Osaka University
Watanabe, Masahiko Hokkaido University
Manabe, Toshiya The University of Tokyo
Yamamoto, Tadashi The University of Tokyo|Okinawa Institute of Science and Technology Graduate University
Takeda, Masatoshi Osaka University
Kano, Masanobu The University of Tokyo
資料タイプ
学術雑誌論文
抄録
Intracellular trafficking of receptor proteins is essential for neurons to detect various extracellular factors during the formation and refinement of neural circuits. However, the precise mechanisms underlying the trafficking of neurotrophin receptors to synapses remain elusive. Here, we demonstrate that a brain-enriched sorting nexin, ARHGAP33, is a new type of regulator for the intracellular trafficking of TrkB, a high-affinity receptor for brain-derived neurotrophic factor. ARHGAP33 knockout (KO) mice exhibit reduced expression of synaptic TrkB, impaired spine development and neuropsychiatric disorder-related behavioural abnormalities. These deficits are rescued by specific pharmacological enhancement of TrkB signalling in ARHGAP33 KO mice. Mechanistically, ARHGAP33 interacts with SORT1 to cooperatively regulate TrkB trafficking. Human ARHGAP33 is associated with brain phenotypes and reduced SORT1 expression is found in patients with schizophrenia. We propose that ARHGAP33/SORT1-mediated TrkB trafficking is essential for synapse development and that the dysfunction of this mechanism may be a new molecular pathology of neuropsychiatric disorders.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
7
開始ページ
10594
発行日
2016-02-03
備考
Supplementary Information : ncomms_7_10594_s1.pdf
Corrigendum : https://doi.org/10.1038/ncomms11466
権利情報
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系