Nebulin and Lmod2 are critical for specifying thin-filament length in skeletal muscle.
Nebulin and Lmod2 are critical for specifying thin-filament length in skeletal muscle.
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DOI：
10.1126/sciadv.abc1992
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发表时间：
2020-11
期刊：
影响因子：
13.6
通讯作者：
Granzier H
中科院分区：
文献类型：
--
作者：
Kiss B;Gohlke J;Tonino P;Hourani Z;Kolb J;Strom J;Alekhina O;Smith JE 3rd;Ottenheijm C;Gregorio C;Granzier H
星云蛋白在快速骨骼肌中控制细丝长度，但在优化效率的肌肉中与平滑素-2合作。调节肌肉中的细丝长度对于控制产生能量的肌凝蛋白马达的数量至关重要。巨大的蛋白质星云形成了一条细长的细丝，它与骨骼肌中细丝的长度有关，其功能在很大程度上仍不清楚。本文以Neb基因的整个超重复序列为靶点，研究了星云蛋白在细丝长度调控中的作用；星云被缩短或延长了115 nm。利用高分辨率结构和功能技术研究了其对细丝长度的影响。结果表明，快肌中细丝长度受雾状蛋白长度的严格调控。在慢肌类型中，星云蛋白的控制不那么严格，在慢肌类型中存在远端无星云蛋白的细丝段，其长度被发现由leiomotin -2 （Lmod2）调节。我们认为星云的严格长度控制促进了高速缩短，星云/Lmod2的双重调节提高了收缩效率。
Nebulin rules thin-filament length in fast skeletal muscle but collaborates with leiomodin-2 in muscles optimized for efficiency. Regulating the thin-filament length in muscle is crucial for controlling the number of myosin motors that generate power. The giant protein nebulin forms a long slender filament that associates along the length of the thin filament in skeletal muscle with functions that remain largely obscure. Here nebulin’s role in thin-filament length regulation was investigated by targeting entire super-repeats in the Neb gene; nebulin was either shortened or lengthened by 115 nm. Its effect on thin-filament length was studied using high-resolution structural and functional techniques. Results revealed that thin-filament length is strictly regulated by the length of nebulin in fast muscles. Nebulin’s control is less tight in slow muscle types where a distal nebulin-free thin-filament segment exists, the length of which was found to be regulated by leiomodin-2 (Lmod2). We propose that strict length control by nebulin promotes high-speed shortening and that dual-regulation by nebulin/Lmod2 enhances contraction efficiency.
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DOI：
10.1038/nrm3510
发表时间：
2013-02
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1083/jcb.201001125
发表时间：
2010-04-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gokhin DS;Lewis RA;McKeown CR;Nowak RB;Kim NE;Littlefield RS;Lieber RL;Fowler VM
通讯作者：
Fowler VM
影响因子：
20.1
作者：
Hidalgo C;Hudson B;Bogomolovas J;Zhu Y;Anderson B;Greaser M;Labeit S;Granzier H
通讯作者：
Granzier H
影响因子：
3
作者：
Buck, Danielle;Hudson, Bryan D.;Granzier, Henk
通讯作者：
Granzier, Henk
影响因子：
3.5
作者：
LABEIT, S;GIBSON, T;TRINICK, J
通讯作者：
TRINICK, J