Arlek M. González-JamettXimena Baez-MatusMaría José OlivaresFernando HinostrozaMaria José Guerra-FernándezJacqueline Vasquez-NavarreteMai Thao BuiPascale GuicheneyNorma Beatriz RomeroJorge A. BevilacquaMarc BitounPablo CaviedesCárdenas, AnaAnaCárdenas2025-12-072025-12-072017-06-2810.1038/s41598-017-04418-w2-s2.0-85021742106https://cris-uv-2.scimago.es/handle/123456789/7343WOS:000425967000002Dynamin-2 is a ubiquitously expressed GTP-Ase that mediates membrane remodeling. Recent findings indicate that dynamin-2 also regulates actin dynamics. Mutations in dynamin-2 cause dominant centronuclear myopathy (CNM), a congenital myopathy characterized by progressive weakness and atrophy of skeletal muscles. However, the muscle-specific roles of dynamin-2 affected by these mutations remain elusive. Here we show that, in muscle cells, the GTP-Ase activity of dynamin-2 is involved in de novo actin polymerization as well as in actin-mediated trafficking of the glucose transporter GLUT4. Expression of dynamin-2 constructs carrying CNM-linked mutations disrupted the formation of new actin filaments as well as the stimulus-induced translocation of GLUT4 to the plasma membrane. Similarly, mature muscle fibers isolated from heterozygous knock-in mice that harbor the dynamin-2 mutation p.R465W, an animal model of CNM, exhibited altered actin organization, reduced actin polymerization and impaired insulin-induced translocation of GLUT4 to the sarcolemma. Moreover, GLUT4 displayed aberrant perinuclear accumulation in biopsies from CNM patients carrying dynamin-2 mutations, further suggesting trafficking defects. These results suggest that dynamin-2 is a key regulator of actin dynamics and GLUT4 trafficking in muscle cells. Our findings also support a model in which impairment of actin-dependent trafficking contributes to the pathological mechanism in dynamin-2-Associated CNM.enacceso abiertoMultidisciplinary SciencesMultidisciplinaryarticle