ATG14 and RB1CC1 play essential roles in maintaining muscle homeostasis
العنوان: | ATG14 and RB1CC1 play essential roles in maintaining muscle homeostasis |
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المؤلفون: | Bo Wang, Peter Vogel, Xiujie Li-Harms, Dongfang Li, Mondira Kundu |
المصدر: | Autophagy |
بيانات النشر: | Taylor & Francis, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | 0301 basic medicine, endocrine system, Cardiomyopathy, Vesicular Transport Proteins, Autophagy-Related Proteins, TARDBP, Pathogenesis, 03 medical and health sciences, Mice, Ubiquitin, Conditional gene knockout, medicine, Autophagy, Animals, Autophagy-Related Protein-1 Homolog, Homeostasis, Molecular Biology, 030102 biochemistry & molecular biology, biology, Brief Report, Muscles, Cell Biology, ULK1, medicine.disease, Cell biology, 030104 developmental biology, biology.protein, TBST |
الوصف: | Defects in macroautophagy/autophagy are implicated in the pathogenesis of neuromuscular and heart diseases. To precisely define the roles of autophagy-related genes in skeletal and cardiac muscles, we generated muscle-specific rb1cc1- and atg14-conditional knockout (cKO) mice by using Ckm/Ckmm2-Cre and compared their phenotypes to those of ulk1 ulk2-conditional double-knockout (cDKO) mice. atg14-cKO mice developed hypertrophic cardiomyopathy, which was associated with abnormal accumulation of autophagic cargoes in the heart and early mortality. Skeletal muscles of both atg14-cKO and rb1cc1-cKO mice showed features of autophagic vacuolar myopathy with ubiquitin(+) SQSTM1(+) deposits, but only those of rb1cc1-cKO mice showed TARDBP/TDP-43(+) pathology and other features of the inclusion body myopathy–like disease we previously described in ulk1 ulk2-cDKO mice. Herein, we highlight tissue-specific differences between skeletal and cardiac muscles in their reliance on core autophagy proteins and unique roles for ULK1-ULK2 and RB1CC1 among these proteins in the development of TARDBP(+) pathology. ABBREVIATIONS:AVM: autophagic vacuolar myopathy; cDKO: conditional double knockout; cKO: conditional knockout; H&E: hematoxylin and eosin; IBM: inclusion body myopathy; mtDNA: mitochondrial DNA; PFA: paraformaldehyde; RNP: ribonucleoprotein; TBST: Tris-buffered saline with 0.2% Triton X-100 |
اللغة: | English |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecc55c88c231d7159dabe26c8b4e3211Test https://europepmc.org/articles/PMC8496527Test/ |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....ecc55c88c231d7159dabe26c8b4e3211 |
قاعدة البيانات: | OpenAIRE |
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