دورية أكاديمية
Downsizing the molecular spring of the giant protein titin reveals that skeletal muscle titin determines passive stiffness and drives longitudinal hypertrophy
| العنوان: | Downsizing the molecular spring of the giant protein titin reveals that skeletal muscle titin determines passive stiffness and drives longitudinal hypertrophy |
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| المؤلفون: | Ambjorn Brynnel, Yaeren Hernandez, Balazs Kiss, Johan Lindqvist, Maya Adler, Justin Kolb, Robbert van der Pijl, Jochen Gohlke, Joshua Strom, John Smith, Coen Ottenheijm, Henk L Granzier |
| المصدر: | eLife, Vol 7 (2018) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | biomechanics, muscle, myofilament function, elasticity, titinopathies, passive stiffness, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Titin, the largest protein known, forms an elastic myofilament in the striated muscle sarcomere. To establish titin’s contribution to skeletal muscle passive stiffness, relative to that of the extracellular matrix, a mouse model was created in which titin’s molecular spring region was shortened by deleting 47 exons, the TtnΔ112-158 model. RNA sequencing and super-resolution microscopy predicts a much stiffer titin molecule. Mechanical studies with this novel mouse model support that titin is the main determinant of skeletal muscle passive stiffness. Unexpectedly, the in vivo sarcomere length working range was shifted to shorter lengths in TtnΔ112-158 mice, due to a ~ 30% increase in the number of sarcomeres in series (longitudinal hypertrophy). The expected effect of this shift on active force generation was minimized through a shortening of thin filaments that was discovered in TtnΔ112-158 mice. Thus, skeletal muscle titin is the dominant determinant of physiological passive stiffness and drives longitudinal hypertrophy.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter). |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/40532; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.40532 |
| URL الوصول: | https://doaj.org/article/8efda138908741c7b765607d2f5a2dd8 |
| رقم الأكسشن: | edsdoj.8efda138908741c7b765607d2f5a2dd8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.40532 |