Proteins of the LINC complex are associated to Emery-Dreifuss muscular dystrophy (EDMD). One of the most interesting components of the LINC complex is SUN1, recently related to nuclear positioning defects in sensory cells of hearing apparatus and previously shown to be causative of myonuclear clustering in EDMD2 muscle cells. In a patient carrying heterozygous compound SUN1 mutations (G68D and G338S), we found for the first time an incomplete EDMD phenotype. Myotubes from this patient displayed defects in myonuclear organization, accompanied by mislocalization of the centromeric protein pericentrin and altered microtubule nucleation in myotubes. Transfection of C2C12 myotubes with SUN1 mutants confirmed delocalization of pericentrin from the nuclear envelope. Our data indicate that SUN1 acts as a disease gene and is involved muscle disease pathogenesis and support the hypothesis that defects in the LINC complex cause muscular dystrophy through disruption of nuclear-microtubule association and myonuclear positioning.
The LINC complex regulates the microtubule network nucleation in human muscle
Mattioli E;
2013
Abstract
Proteins of the LINC complex are associated to Emery-Dreifuss muscular dystrophy (EDMD). One of the most interesting components of the LINC complex is SUN1, recently related to nuclear positioning defects in sensory cells of hearing apparatus and previously shown to be causative of myonuclear clustering in EDMD2 muscle cells. In a patient carrying heterozygous compound SUN1 mutations (G68D and G338S), we found for the first time an incomplete EDMD phenotype. Myotubes from this patient displayed defects in myonuclear organization, accompanied by mislocalization of the centromeric protein pericentrin and altered microtubule nucleation in myotubes. Transfection of C2C12 myotubes with SUN1 mutants confirmed delocalization of pericentrin from the nuclear envelope. Our data indicate that SUN1 acts as a disease gene and is involved muscle disease pathogenesis and support the hypothesis that defects in the LINC complex cause muscular dystrophy through disruption of nuclear-microtubule association and myonuclear positioning.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
