title: Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1.
abstract: Myotubes are syncytial cells generated by fusion of myoblasts. Among the numerous nuclei in myotubes of skeletal muscle fibres, the majority are equidistantly positioned at the periphery, except for clusters of multiple nuclei underneath the motor endplate. The correct positioning of nuclei is thought to be important for muscle function and requires nesprin-1 (also known as SYNE1), a protein of the nuclear envelope. Consistent with this, mice lacking functional nesprin-1 show defective nuclear positioning and present aspects of Emery-Dreifuss muscular dystrophy. In this study, we perform small interfering RNA (siRNA) experiments in C2C12 myoblasts undergoing differentiation, demonstrating that the positioning of nuclei requires PCM-1, a protein of the centrosome that relocalizes to the nuclear envelope at the onset of differentiation in a manner that is dependent on the presence of nesprin-1. PCM-1 itself is required for recruiting proteins of the dynein-dynactin complex and of kinesin motor complexes. This suggests that microtubule motors that are attached to the nuclear envelope support the movement of nuclei along microtubules, to ensure their correct positioning in the myotube.
authors: Centre de Biologie du Développement, Université Paul Sabatier/CNRS, Toulouse 31062, France.
authors: Aude
authors: 0000-0001-8801-2951
authors: A
authors: Espigat-Georger
authors: Centre de Biologie du Développement, Université Paul Sabatier/CNRS, Toulouse 31062, France.
authors: Vyacheslav
authors: V
authors: Dyachuk
authors: Centre de Biologie du Développement, Université Paul Sabatier/CNRS, Toulouse 31062, France.
authors: Cécile
authors: C
authors: Chemin
authors: Centre de Biologie du Développement, Université Paul Sabatier/CNRS, Toulouse 31062, France.
authors: Laurent
authors: L
authors: Emorine
authors: Centre de Biologie du Développement, Université Paul Sabatier/CNRS, Toulouse 31062, France andreas.merdes@univ-tlse3.fr.
authors: Andreas
authors: 0000-0002-3739-2728
authors: A
authors: Merdes
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D002645:Chickens; D003598:Cytoskeletal Proteins; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C490114:Pcm1 protein, mouse; C485901:Syne1 protein, mouse
keywords: Centrosome protein; Myotube; Nesprin; Nuclear positioning