PT  - JOURNAL ARTICLE
AU  - Kiss, Balázs
AU  - Gohlke, Jochen
AU  - Tonino, Paola
AU  - Hourani, Zaynab
AU  - Kolb, Justin
AU  - Strom, Joshua
AU  - Alekhina, Olga
AU  - Smith, John E.
AU  - Ottenheijm, Coen
AU  - Gregorio, Carol
AU  - Granzier, Henk
TI  - Nebulin and Lmod2 are critical for specifying thin-filament length in skeletal muscle
AID  - 10.1126/sciadv.abc1992
DP  - 2020 Nov 01
TA  - Science Advances
PG  - eabc1992
VI  - 6
IP  - 46
4099  - http://advances.sciencemag.org/content/6/46/eabc1992.short
4100  - http://advances.sciencemag.org/content/6/46/eabc1992.full
SO  - Sci Adv2020 Nov 01; 6
AB  - 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.