Thin filament length regulation in striated muscle sarcomeres: pointed-end dynamics go beyond a nebulin ruler.

Thin filament length regulation in striated muscle sarcomeres: pointed-end dynamics go beyond a nebulin ruler.
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DOI:
10.1016/j.semcdb.2008.08.009
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发表时间:
2008-12
影响因子:
7.3
通讯作者:
Fowler VM
Fowler VM
中科院分区:
生物学2区
文献类型:
--
作者:
Littlefield RS;Fowler VM

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横纹肌中的肌动蛋白(细)丝受到高度调节,并在长度上精确指定,以最佳地与肌球蛋白(粗)丝重叠,从而有效地收缩肌原纤维。在这里,我们回顾并批判性地讨论了最近关于脊椎动物骨骼、脊椎动物心脏和无脊椎动物(节肢动物)肌节如何控制细丝长度的证据。覆盖蛋白原调节蛋白对生长缓慢(尖端)末端的肌动蛋白聚合动力学的调节为细丝长度如何在所有三种肌肉类型中得到生理优化提供了统一的解释。NeBulin是一种大型蛋白质,被认为通过尺子机制指定脊椎动物骨骼肌中细纤维的长度,它可能不会直接控制尖端肌动蛋白的动态,而是可能稳定细纤维的一个大核心区域。我们认为,这种对星云蛋白的稳定作用改变了主要由尖端肌动蛋白动力学指定的长度,从而在脊椎动物骨骼肌中产生了统一的细丝长度。我们认为,星云是星云蛋白的一种小同系物,可以稳定相应较短的核心区域,并允许单个细丝长度根据脊椎动物心肌中工作肌节的长度而变化。我们提出了一个统一的细丝长度调节模型,其中这两种机制协同工作,为不同肌肉的特定收缩环境量身定做细丝长度。
The actin (thin) filaments in striated muscle are highly regulated and precisely specified in length to optimally overlap with the myosin (thick) filaments for efficient myofibril contraction. Here, we review and critically discuss recent evidence for how thin filament lengths are controlled in vertebrate skeletal, vertebrate cardiac, and invertebrate (arthropod) sarcomeres. Regulation of actin polymerization dynamics at the slow-growing (pointed) ends by the capping protein tropomodulin provides a unified explanation for how thin filament lengths are physiologically optimized in all three muscle types. Nebulin, a large protein thought to specify thin filament lengths in vertebrate skeletal muscle through a ruler mechanism, may not control pointed-end actin dynamics directly, but instead may stabilize a large core region of the thin filament. We suggest that this stabilizing function for nebulin modifies the lengths primarily specified by pointed-end actin dynamics to generate uniform filament lengths in vertebrate skeletal muscle. We suggest that nebulette, a small homolog of nebulin, may stabilize a correspondingly shorter core region and allow individual thin filament lengths to vary according to working sarcomere lengths in vertebrate cardiac muscle. We present a unified model for thin filament length regulation where these two mechanisms cooperate to tailor thin filament lengths for specific contractile environments in diverse muscles.
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