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Nebulin and Titin Modulate Cross-bridge Cycling and Length-dependent Calcium Sensitivity

Mijailovich, Srboljub M., Stojanovic, Boban, Nedic, Djordje, Svicevic, Marina, Geeves, Michael A., Irving, Thomas C., Granzier, Henk L. (2019) Nebulin and Titin Modulate Cross-bridge Cycling and Length-dependent Calcium Sensitivity. The Journal of General Physiology, . ISSN 0022-1295. (doi:10.1085/jgp.201812165)

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Abstract

Various mutations in the structural proteins nebulin and titin that are present in human disease are known

length and impairment of myosin binding to actin, whereas titin is thought to regulate muscle passive

modulation of muscle function by these sarcomeric proteins by using the computational platform

of crossbridge cycling, and calcium sensitivity of the thin filaments. The simulations show that variation

nebulin-deficient muscle, but instead must be accompanied by a decreased myosin binding rate.

needed to be increased. Simulations for cardiac muscle provided quantitative estimates of the effects of

sarcomere length and inter-filament lattice spacing. Predicted force-pCa relations showed a decrease in

conclude that this behavior is caused by partial redistribution of the muscle load between active muscle

together modulate the release of TnI from actin. These data help advance understanding of how nebulin

and titin mutations affect muscle function.

Item Type: Article
DOI/Identification number: 10.1085/jgp.201812165
Uncontrolled keywords: MUSICO platform, thin filament regulation, 3D explicit lattice, calcium sensitivity, mutation of sarcomeric proteins, skeletal muscle, cardiac muscle
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Michael Geeves
Date Deposited: 08 Apr 2019 12:45 UTC
Last Modified: 03 Jun 2019 09:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/73410 (The current URI for this page, for reference purposes)
Geeves, Michael A.: https://orcid.org/0000-0002-9364-8898
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