Academic Journal
MANF regulates neuronal survival and UPR through its ER-located receptor IRE1α
| العنوان: | MANF regulates neuronal survival and UPR through its ER-located receptor IRE1α |
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| المؤلفون: | Kovaleva, Vera, Yu, Li-Ying, Ivanova, Larisa, Shpironok, Olesya, Nam, Jinhan, Eesmaa, Ave, Kumpula, Esa-Pekka, Sakson, Sven, Toots, Urve, Ustav, Mart, Huiskonen, Juha T., Voutilainen, Merja H., Lindholm, Päivi, Karelson, Mati, Saarma, Mart |
| المساهمون: | Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, Division of Pharmacology and Pharmacotherapy, Regenerative Neuroscience, Laboratory of Structural Biology, Molecular and Integrative Biosciences Research Programme, Helsinki Institute of Sustainability Science (HELSUS), Drug Research Program, Divisions of Faculty of Pharmacy, Mart Saarma / Principal Investigator |
| بيانات النشر: | Cell Press |
| سنة النشر: | 2023 |
| المجموعة: | Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: | Neurosciences, Endoplasmic-reticulum stress, Unfolded protein response, Neurotrophic factor, Transmembrane protein, Kappa-b, Beta, Activation, Model, Proliferation, Homeostasis |
| الوصف: | Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-located pro-tein with cytoprotective effects in neurons and pancreatic b cells in vitro and in models of neurodegeneration and diabetes in vivo. However, the exact mode of MANF action has remained elusive. Here, we show that MANF directly interacts with the ER transmembrane unfolded protein response (UPR) sensor IRE1a, and we identify the binding interface between MANF and IRE1a. The expression of wild-type MANF, but not its IRE1a binding-deficient mutant, attenuates UPR signaling by decreasing IRE1a oligomerization; phosphor-ylation; splicing of Xbp1, Atf6, and Txnip levels; and protecting neurons from ER stress-induced death. MANF-IRE1a interaction and not MANF-BiP interaction is crucial for MANF pro-survival activity in neurons in vitro and is required to protect dopamine neurons in an animal model of Parkinson's disease. Our data show IRE1a as an intracellular receptor for MANF and regulator of neuronal survival. ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| ردمك: | 978-85-14-97501-4 85-14-97501-3 |
| تدمد: | 36739529 |
| Relation: | http://hdl.handle.net/10138/354614; 85149750137; 000931679000001 |
| الاتاحة: | http://hdl.handle.net/10138/354614 |
| Rights: | cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| رقم الانضمام: | edsbas.B1054ECE |
| قاعدة البيانات: | BASE |
| ردمك: | 9788514975014 8514975013 |
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| تدمد: | 36739529 |