Pathological mechanisms of vacuolar aggregate myopathy arising from a Casq1 mutation
| العنوان: | Pathological mechanisms of vacuolar aggregate myopathy arising from a Casq1 mutation |
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| المؤلفون: | Lyle Babcock, Hui J. Wang, Joseph Recio, Amy D. Hanna, Susan L. Hamilton, Chang Seok Lee |
| المصدر: | FASEB J |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Protein aggregation, medicine.disease_cause, Calsequestrin, Biochemistry, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Muscular Diseases, Genetics, medicine, Protein biosynthesis, Animals, Muscle, Skeletal, Myopathy, Molecular Biology, Mutation, Chemistry, Endoplasmic reticulum, Calcium-Binding Proteins, Endoplasmic Reticulum Stress, Cell biology, Lysosomal Storage Diseases, Sarcoplasmic Reticulum, 030104 developmental biology, Proteasome, Unfolded protein response, Calcium, medicine.symptom, 030217 neurology & neurosurgery, Biotechnology |
| الوصف: | Mice with a mutation (D244G, DG) in calsequestrin 1 (CASQ1), analogous to a human mutation in CASQ1 associated with a delayed onset human myopathy (vacuolar aggregate myopathy), display a progressive myopathy characterized by decreased activity, decreased ability of fast twitch muscles to generate force and low body weight after one year of age. The DG mutation causes CASQ1 to partially dissociate from the junctional sarcoplasmic reticulum (SR) and accumulate in the endoplasmic reticulum (ER). Decreased junctional CASQ1 reduces SR Ca(2+) release. Muscles from older DG mice display ER stress, ER expansion, increased mTOR signaling, inadequate clearance of aggregated proteins by the proteasomes, and elevation of protein aggregates and lysosomes. This study suggests that the myopathy associated with the D244G mutation in CASQ1 is driven by CASQ1 mislocalization, reduced SR Ca(2+) release, CASQ1 misfolding/aggregation and ER stress. The subsequent maladaptive increase in protein synthesis and decreased protein aggregate clearance are likely to contribute to disease progression. |
| تدمد: | 1530-6860 0892-6638 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ba44a3d5e2443c5411a90de272c22b9Test https://doi.org/10.1096/fj.202001653rrTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4ba44a3d5e2443c5411a90de272c22b9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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