Contractile myofiber units are mainly composed of thick myosin and thin actin (F-actin) filaments. F-Actin interacts with Microtubule Associated Monooxygenase, Calponin And LIM Domain Containing 2 (MICAL2). Indeed, MICAL2 modifies actin subunits and promotes actin filament turnover by severing them and preventing repolymerization. In this study, we found that MICAL2 increases during myogenic differentiation of adult and pluripotent stem cells (PSCs) towards skeletal, smooth and cardiac muscle cells and localizes in the nucleus of acute and chronic regenerating muscle fibers. In vivo delivery of Cas9-Mical2 guide RNA complexes results in muscle actin defects and demonstrates that MICAL2 is essential for skeletal muscle homeostasis and functionality. Conversely, MICAL2 upregulation shows a positive impact on skeletal and cardiac muscle commitments. Taken together these data demonstrate that modulations of MICAL2 have an impact on muscle filament dynamics and its fine-tuned balance is essential for the regeneration of muscle tissues.
MICAL2 is essential for myogenic lineage commitment / N. Giarratana, F. Conti, R. La Rovere, R. Gijsbers, P. Carai, R. Duelen, T. Vervliet, G. Bultynck, F. Ronzoni, R. Piciotti, D. Costamagna, S. Fulle, I. Barravecchia, D. Angeloni, Y. Torrente, M. Sampaolesi. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 11:8(2020 Aug 18).
|Titolo:||MICAL2 is essential for myogenic lineage commitment.|
GIARRATANA, NEFELE (Primo) [Writing – Original Draft Preparation]
TORRENTE, YVAN (Penultimo) [Conceptualization]
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Data di pubblicazione:||18-ago-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/s41419-020-02886-z|
|Appare nelle tipologie:||01 - Articolo su periodico|