Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons
| العنوان: | Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons |
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| المؤلفون: | Takeshi Onoue, Yoshihiro Ito, Hirotaka Sakamoto, Takashi Miyata, Yuichi Hodai, Nobuhiko Ohno, Tsutomu Miwata, Kazuki Mitsumoto, Shintaro Iwama, Hajime Ozaki, Hiroshi Arima, Junki Kurimoto, Daisuke Hagiwara, Natsuko Kawakami, Mami Matsumoto, Tomoko Kobayashi, Ryoichi Banno, Hidetaka Suga, Hiroshi Takagi, Yohei Kawaguchi, Mariko Sugiyama |
| المصدر: | iScience, Vol 23, Iss 10, Pp 101648-(2020) iScience |
| بيانات النشر: | Cell Press, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Vasopressin, Multidisciplinary, Arginine, Chemistry, Endoplasmic reticulum, Mutant, technical aspects of cell biology, Chromosomal translocation, 02 engineering and technology, Protein aggregation, 021001 nanoscience & nanotechnology, Article, Cell biology, neuroscience, 03 medical and health sciences, 030104 developmental biology, Membrane, Mutant protein, cell biology, lcsh:Q, lcsh:Science, 0210 nano-technology |
| الوصف: | Summary Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER. Graphical Abstract Highlights • Mutant AVP precursors are confined to ERACs connected to the ER of FNDI AVP neurons • Lysosomes fuse with ERACs surrounded by phagophore-like membranes • Lysosome-related molecules are localized within ERACs • Rapamycin reduces and chloroquine increases protein aggregate accumulation in ERACs neuroscience; cell biology; technical aspects of cell biology |
| اللغة: | English |
| تدمد: | 2589-0042 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0c9254ad64e4ea5742fcefdcc26ed869 https://ousar.lib.okayama-u.ac.jp/61154 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0c9254ad64e4ea5742fcefdcc26ed869 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 25890042 |
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