Altered cross-bridge properties in skeletal muscle dystrophies.

Aziz Guellich,Catherine Coirault,Alexandre Demoule,Elisa Negroni,Valã©Rie Decostre

doi:10.3389/fphys.2014.00393

Abstract

Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca2+ through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies (MDs) have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal MDs and discuss their ultimate impacts on striated muscle function.

Highlights

Muscular dystrophies (MDs) are a group of more than 30 clinical and molecular heterogeneous genetic disorders that cause progressive degeneration of the skeletal muscle fibers
The present review focuses on the changes in the function of contractile proteins and in CB performance that may occur in the context of skeletal muscle dystrophies (MDs) and their contribution to the pathophysiological mechanisms of these diseases
DIRECTIONS The mechanisms of muscle weakness have been a fundamental question of the physiopathology of muscle dystrophy for more than 50 years

Summary

INTRODUCTION

Muscular dystrophies (MDs) are a group of more than 30 clinical and molecular heterogeneous genetic disorders that cause progressive degeneration of the skeletal muscle fibers. They are characterized by severe muscle weakness that generally affects limb, axial, and/or facial muscles to a variable extent. The present review focuses on the changes in the function of contractile proteins and in CB performance that may occur in the context of skeletal muscle dystrophies (MDs) and their contribution to the pathophysiological mechanisms of these diseases

CYCLICAL INTERACTIONS OF ACTIN WITH MYOSIN

MODULATIONS AND DAMAGE OF CB KINETICS BY OXIDATIVE STRESS

CONCLUSIONS AND FUTURE DIRECTIONS