Signaling pathways in activity-dependent fiber type plasticity in adult skeletal muscle
Signaling pathways in activity-dependent fiber type plasticity in adult skeletal muscle
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DOI：
10.1007/s10974-005-9002-0
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发表时间：
2005-02-01
影响因子：
2.7
通讯作者：
Schneider, MF
中科院分区：
文献类型：
--
作者：
Liu, YW;Shen, TS;Schneider, MF
由于大多数肌肉蛋白的异构体和表达量的不同，成人的快抽动和慢抽动的骨骼肌纤维在功能特性上表现出特征性的差异。然而，这些差异可以通过对失神经肌肉的慢性电刺激而逆转，这种模式是其他类型纤维的典型模式。在这里，我们回顾了三种可能的信号通路，它们可能有助于纤维类型从快到慢的转变。第一种途径是由于胞浆内[Ca~(2+)]升高而激活胞浆内钙敏感的钙调神经磷酸酶钙调神经磷酸酶(CaN)，导致胞浆内NFATc去磷酸化，使去磷酸化的NFATc从胞浆移位到胞核，并激活胞核中慢纤维基因的表达。第二种途径是核内[Ca~(2+)]升高，导致核内钙调蛋白依赖性蛋白激酶的激活，使核内的HDAC磷酸化，从而允许HDAC的核外流，从而降低HDAC对慢纤维基因表达的MEF2激活的抑制作用。第三个可能的途径涉及CaN的核进入，核内MEF2的去磷酸化，以及随后去磷酸化的MEF2增加慢纤维型基因表达的激活。简要回顾了我们对成人快速抽动骨骼肌纤维研究中发现的前两条途径的证据。
Adult fast- and slow-twitch skeletal muscle fibers exhibit characteristic differences in functional properties due to differences in the isoforms and quantities of expression of most muscle proteins. However, these differences may be reversed by chronic electrical stimulation of denervated muscle with the pattern typical of the other fiber type. Here, we review three possible signaling pathways that may contribute to fast to slow fiber type transformation. The first pathway involves cytosolic activation of the Ca2+ sensitive posphatase calcineurin (CaN) due to elevated cytosolic [Ca2+], resulting in dephosphorylation of cytoplasmic NFATc, translocation of dephosphorylated NFATc from cytoplasm into the nucleus and activation of slow fiber gene expression by NFATc in the nucleus. The second pathway involves elevated intranuclear [Ca2+] causing the activation of nuclear calmodulin dependent protein kinase, which phosphorylates HDAC within the nucleus and thereby permits nuclear efflux of HDAC, thus decreasing the HDAC suppression of MEF2 activation of slow fiber gene expression. The third possible pathway involves nuclear entry of CaN, dephosphorylation of intranuclear MEF2 and consequent increased activation of slow fiber type gene expression by dephosphorylated MEF2. Evidence for the first two pathways from our studies on adult fast twitch skeletal muscle fibers is briefly reviewed.