Accumulation of muscle ankyrin repeat protein transcript reveals local activation of primary myotube endcompartments during muscle morphogenesis.
Accumulation of muscle ankyrin repeat protein transcript reveals local activation of primary myotube endcompartments during muscle morphogenesis.
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DOI：
10.1083/jcb.139.5.1231
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发表时间：
1997-12-01
期刊：
影响因子：
--
通讯作者：
Caroni P
中科院分区：
文献类型：
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作者：
Baumeister A;Arber S;Caroni P
在肌肉形态发生的过程中，响应于来自周围间充质的图案化信息，建立了每一个体身体肌肉的特征形状和位置。在整个肌肉形态发生过程中，初级肌管排列成平行的小束，每个肌管从头到尾横跨形成的肌肉。这种独特的安排潜在地赋予了初级肌管末端区域对肌肉形态发生的关键作用。我们克隆了肌肉骨架蛋白重复蛋白(MARP)，它是成年大鼠骨骼肌失神经后诱导表达的基因。MARP是人类C-193(Chu，W.，D.K.Burns，R.A.Swerick和D.H.Presky)的啮齿动物同源物。1995年。J.Biol.化学。270：10236-10245)，与大鼠心脏强直蛋白重复蛋白相同。邹勇，S.Evans，J.Chen，郭海昌，R.P.Harvey，K.R.Chien。1997年。发展。124：793-804)。在失神经肌肉纤维中，MARP转录本以一种独特的突触周围模式积累。MARP在大血管和心肌中也有表达，心肌肥厚可进一步诱导MARP表达。在胚胎发育过程中，MARP在骨骼肌的形成中表达。小鼠胚胎的原位杂交分析表明，在肌肉形态发生过程中，MARP转录本仅在初级肌管的末端积累。这与血栓反应蛋白-4在相邻肌腱间充质中的表达密切相关，提示这两个肌间充质可能构成了参与肌肉形态发生的功能单位。转基因实验证实，MARP蛋白在细胞核内积聚，MARP的mRNA和蛋白水平均受调控早期反应基因的快速降解机制控制。这些结果证实了与肌肉形态发生和失神经支配相关的新的调节肌肉纤维亚室的存在，并提示MARP可能是从预期的肌腱间充质到形成肌肉的局部信号通路以及从激活的肌肉间质细胞到失神经肌肉纤维的局部信号通路中的关键核辅因子。
The characteristic shapes and positions of each individual body muscle are established during the process of muscle morphogenesis in response to patterning information from the surrounding mesenchyme. Throughout muscle morphogenesis, primary myotubes are arranged in small parallel bundles, each myotube spanning the forming muscles from end to end. This unique arrangement potentially assigns a crucial role to primary myotube end regions for muscle morphogenesis. We have cloned muscle ankyrin repeat protein (MARP) as a gene induced in adult rat skeletal muscle by denervation. MARP is the rodent homologue of human C-193 (Chu, W., D.K. Burns, R.A. Swerick, and D.H. Presky. 1995. J. Biol. Chem. 270:10236–10245) and is identical to rat cardiac ankyrin repeat protein. (Zou, Y., S. Evans, J. Chen, H.-C. Kuo, R.P. Harvey, and K.R. Chien. 1997. Development. 124:793–804). In denervated muscle fibers, MARP transcript accumulated in a unique perisynaptic pattern. MARP was also expressed in large blood vessels and in cardiac muscle, where it was further induced by cardiac hypertrophy. During embryonic development, MARP was expressed in forming skeletal muscle. In situ hybridization analysis in mouse embryos revealed that MARP transcript exclusively accumulates at the end regions of primary myotubes during muscle morphogenesis. This closely coincided with the expression of thrombospondin-4 in adjacent prospective tendon mesenchyme, suggesting that these two compartments may constitute a functional unit involved in muscle morphogenesis. Transfection experiments established that MARP protein accumulates in the nucleus and that the levels of both MARP mRNA and protein are controlled by rapid degradation mechanisms characteristic of regulatory early response genes. The results establish the existence of novel regulatory muscle fiber subcompartments associated with muscle morphogenesis and denervation and suggest that MARP may be a crucial nuclear cofactor in local signaling pathways from prospective tendon mesenchyme to forming muscle and from activated muscle interstitial cells to denervated muscle fibers.