MICAL2 is essential for myogenic lineage commitment

Nefele Giarratana, Filippo Conti, Rita La Rovere, Rik Gijsbers, Paolo Carai, Robin Duelen, Tim Vervliet, Geert Bultynck, Flavio Ronzoni, Roberto Piciotti, Domiziana Costamagna, Stefania Fulle (+4 others)
2020 Cell Death and Disease  
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
more » ... lls 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.
doi:10.1038/s41419-020-02886-z pmid:32811811 fatcat:26eaf4kesngfjhfglj2p5dam64