First Author | Kiss B | Year | 2020 |
Journal | Sci Adv | Volume | 6 |
Issue | 46 | PubMed ID | 33177085 |
Mgi Jnum | J:331852 | Mgi Id | MGI:6800249 |
Doi | 10.1126/sciadv.abc1992 | Citation | Kiss B, et al. (2020) Nebulin and Lmod2 are critical for specifying thin-filament length in skeletal muscle. Sci Adv 6(46) |
abstractText | 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. |