کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3001349 1180621 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The calcineurin-NFAT pathway controls activity-dependent circadian gene expression in slow skeletal muscle
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی سیستم های درون ریز و اتونومیک
پیش نمایش صفحه اول مقاله
The calcineurin-NFAT pathway controls activity-dependent circadian gene expression in slow skeletal muscle
چکیده انگلیسی


• Activity is a major extrinsic factor driving ∼15% of muscle circadian genes.
• Calcineurin-NFAT drives activity-dependent circadian gene expression in muscle.
• The majority of skeletal muscle circadian genes are muscle type-specific.
• A common set of skeletal muscle circadian genes are clock-dependent.

ObjectivePhysical activity and circadian rhythms are well-established determinants of human health and disease, but the relationship between muscle activity and the circadian regulation of muscle genes is a relatively new area of research. It is unknown whether muscle activity and muscle clock rhythms are coupled together, nor whether activity rhythms can drive circadian gene expression in skeletal muscle.MethodsWe compared the circadian transcriptomes of two mouse hindlimb muscles with vastly different circadian activity patterns, the continuously active slow soleus and the sporadically active fast tibialis anterior, in the presence or absence of a functional skeletal muscle clock (skeletal muscle-specific Bmal1 KO). In addition, we compared the effect of denervation on muscle circadian gene expression.ResultsWe found that different skeletal muscles exhibit major differences in their circadian transcriptomes, yet core clock gene oscillations were essentially identical in fast and slow muscles. Furthermore, denervation caused relatively minor changes in circadian expression of most core clock genes, yet major differences in expression level, phase and amplitude of many muscle circadian genes.ConclusionsWe report that activity controls the oscillation of around 15% of skeletal muscle circadian genes independently of the core muscle clock, and we have identified the Ca2+-dependent calcineurin-NFAT pathway as an important mediator of activity-dependent circadian gene expression, showing that circadian locomotor activity rhythms drive circadian rhythms of NFAT nuclear translocation and target gene expression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Metabolism - Volume 4, Issue 11, November 2015, Pages 823–833
نویسندگان
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