Nebulin and Lmod2 are critical for specifying thin-filament length in skeletal muscle

Balázs Kiss, Jochen Gohlke, Paola Tonino, Zaynab Hourani, Justin Kolb, Joshua Strom, Olga Alekhina, John E. Smith, Coen A.C. Ottenheijm, Carol Gregorio, Henk Granzier*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbereabc1992
JournalScience Advances
Volume6
Issue number46
DOIs
Publication statusPublished - 11 Nov 2020

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