Description

Abstract

Muscle cells are characterized by the presence of several nuclei regularly spaced beneath the plasma membrane. Whether this particular arrangement is necessary for muscle function is still under discussion. Nevertheless, several muscle diseases are characterized by abnormal nuclear positioning, including centronuclear myopathies, titinopathies and desminopathies, or diseases caused by mutations in nuclear-envelope proteins known to be involved in nuclear movement in other systems.

For several years, we have studied the mechanisms controlling three of the four successive and distinct nuclear movements that occur during myofiber formation, using live imaging. By screening the effects of depleting different molecular motors, we identified several microtubule-associated motors involved at different levels in nuclear movement and positioning. We established that the connection between the nucleus and the cytoskeleton is decisive for proper nuclear positioning. In particular, Nesprin-1, a protein mutated in a congenital muscular dystrophy, is required for microtubule cytoskeleton reorganization during muscle-cell differentiation and for subsequent nuclear movements. We are currently studying the involvement of nuclear deformation and nuclear-envelope composition in muscle differentiation. Our research uses in vitro systems that recapitulate in vivo observations and make it possible to study the effects of mutations found in muscle diseases on nuclear positioning in muscle cells.