| Item type |
文献 / Documents(1) |
| 公開日 |
2020-05-11 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1016/j.bbrc.2020.03.019 |
|
|
言語 |
ja |
|
|
関連名称 |
10.1016/j.bbrc.2020.03.019 |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| タイトル |
|
|
タイトル |
Implications of graded reductions in CLN6’s anti-aggregate activity for the development of the neuronal ceroid lipofuscinoses |
|
言語 |
en |
| 著者 |
ヤマシタ, アリサ
シロ, ユウキ
ヒラキ, ユリ
ユジリ, タカトシ
山﨑, 哲男
|
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
CLN6, spanning the endoplasmic reticulum transmembrane, is a protein of unknown function. Mutations in the CLN6 gene are linked to an autosomal recessively inherited disorder termed CLN6 disease, classified as a form of the neuronal ceroid lipofuscinoses (NCL). The pathogenesis of CLN6 disease remains poorly understood due to a lack of information about physiological roles CLN6 plays. We previously demonstrated that CLN6 has the ability to prevent protein aggregate formation, and thus hypothesized that the abrogation of CLN6’s anti-aggregate activity underlies the development of CLN6 disease. To test this hypothesis, we narrowed down the region vital for CLN6’s anti-aggregate activity, and subsequently investigated if pathogenic mutations within the region attenuate CLN6’s anti-aggregate activity toward four aggregation-prone αB-crystallin (αBC) mutants. None of the four αBC mutants was prevented from aggregating by the Arg106ProfsX truncated CLN6 mutant, the human counterpart of the nclf mutant identified in a naturally occurring mouse model of late infantile-onset CLN6 disease. In contrast, the Arg149Cys and the Arg149His CLN6 mutants, both associated with adult-onset CLN6 disease, blocked aggregation of two out of and all of the four αBC mutants, respectively, indicating that CLN6’s anti-aggregate activity is differentially modulated according to the substitution pattern at the same amino acid position. Collectively, we here propose that the graded reduction in CLN6’s anti-aggregate activity governs the clinical course of late infantile- and adult- onset NCL. |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
CLN6 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
NCL |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
ER |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Kufs |
| 書誌情報 |
en : Biochemical and Biophysical Research Communications
巻 525,
号 4,
p. 883-888,
発行日 2020-03-11
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0006291X |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00564395 |
| 収録物ID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA11542044 |
| 出版者 |
|
|
出版者 |
Elsevier |
|
言語 |
en |
| 権利情報 |
|
|
言語 |
en |
|
権利情報 |
© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| EID |
|
|
識別子 |
365262 |
|
識別子タイプ |
URI |
| 言語 |
|
|
言語 |
eng |
bbrc_525_4_883.pdf (1020 KB)
