T-tubule alterations and muscle weakness in myotonic dystrophy

Model of T-tubule alterations and muscle weakness in myotonic dystrophic patients. In DM, expanded CUG or CCUG repeats sequester MBNL1 within intranuclear aggregates, resulting in decrease levels of free MBNL1 available to regulate alternative splicing. Consequently, the exon 11 of BIN1 pre-mRNA, which is normally included in adult skeletal muscle, is skipped in DM patients and results in expression of a fetal isoform of BIN1 unable to bind to PtdIns5P and to tubulate membranes, leading to misorganization of the T-tubule network and alteration of the excitation-contraction (E-C) coupling.