Defective Acetylcholine Receptor Subunit Switch Precedes Atrophy of Slow-Twitch Skeletal Muscle Fibers Lacking ERK1/2 Kinases in Soleus Muscle.
Defective Acetylcholine Receptor Subunit Switch Precedes Atrophy of Slow-Twitch Skeletal Muscle Fibers Lacking ERK1/2 Kinases in Soleus Muscle.
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DOI：
10.1038/srep38745
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发表时间：
2016-12-09
影响因子：
4.6
通讯作者：
Rimer M
中科院分区：
文献类型：
--
作者：
Wang S;Seaberg B;Paez-Colasante X;Rimer M
为了测试细胞外信号调节激酶1和2（ERK1/2）在慢肌、1型骨骼肌纤维中的作用，我们研究了肌纤维ERK1/2基因缺陷小鼠的比目鱼肌。年轻成年突变型比目鱼肌严重萎缩，1型纤维高度萎缩，大多数突触部位去神经支配，“胎儿”乙酰胆碱受体γ亚单位（AChRγ）诱导表达，“成人”AChRε减少，线粒体生物发生和功能受损。在断奶幼鼠中，纤维形态和线粒体标志物大多正常，但观察到AChRγ上调和AChRε下调。断奶幼鼠肌肉中具有胎儿型AChRs的突触部位在对照组中约为3%，在突变体中约为40%，后者大多数位于1型纤维上。这些结果表明：（1）ERK1/2对慢肌纤维生长至关重要；（2）有缺陷的γ/ε - AChR亚单位转换，优先发生在慢肌纤维的突触处，先于突变型比目鱼肌的萎缩；（3）去神经支配可能导致这种萎缩，以及（4）神经肌肉突触是体内肌肉ERK1/2功能的主要亚细胞靶点。
To test the role of extracellular-signal regulated kinases 1 and 2 (ERK1/2) in slow-twitch, type 1 skeletal muscle fibers, we studied the soleus muscle in mice genetically deficient for myofiber ERK1/2. Young adult mutant soleus was drastically wasted, with highly atrophied type 1 fibers, denervation at most synaptic sites, induction of “fetal” acetylcholine receptor gamma subunit (AChRγ), reduction of “adult” AChRε, and impaired mitochondrial biogenesis and function. In weanlings, fiber morphology and mitochondrial markers were mostly normal, yet AChRγ upregulation and AChRε downregulation were observed. Synaptic sites with fetal AChRs in weanling muscle were ~3% in control and ~40% in mutants, with most of the latter on type 1 fibers. These results suggest that: (1) ERK1/2 are critical for slow-twitch fiber growth; (2) a defective γ/ε-AChR subunit switch, preferentially at synapses on slow fibers, precedes wasting of mutant soleus; (3) denervation is likely to drive this wasting, and (4) the neuromuscular synapse is a primary subcellular target for muscle ERK1/2 function in vivo.
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影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
DOI：
10.1083/jcb.200210117
发表时间：
2003-05-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nicole S;Desforges B;Millet G;Lesbordes J;Cifuentes-Diaz C;Vertes D;Cao ML;De Backer F;Languille L;Roblot N;Joshi V;Gillis JM;Melki J
通讯作者：
Melki J
影响因子：
14.5
作者：
Gattenlöhner, S;Schneider, C;Marx, A
通讯作者：
Marx, A
麝香诱导神经肌肉突触形成中的关键基因的新途径。
影响因子：
7.8
作者：
Lacazette, E;Le Calvez, S;Gajendran, N;Brenner, HR
通讯作者：
Brenner, HR
影响因子：
64.8
作者：
MISHINA, M;TAKAI, T;SAKMANN, B
通讯作者：
SAKMANN, B