On the footsteps of Triadin and its role in skeletal muscle

Figure 1 Genomic structure of mouse Trdn gene. A: Schematic representation of mouse Triadin cDNA structure within the context of the Triadin genomic locus according to the Mouse Genomic Informatics (MGI) gene model[60]; B: Splicing patterns of Triadin. Exons are shown as boxes and introns as lines. The exon splicing pattern that gives rise to the three cardiac Triadin isoforms currently cloned (MT1, MT2 and MT3) as well as the predicted full-length skeletal isoform (Trdn95) are indicated. Size and number of exon boxes in the genomic locus (blue) are not showed in actual scale.

Figure 2 Proposed model of Ca²⁺ regulation by Triadin in wild-type and Triadin-null skeletal muscle. Lack of Triadin binding to type-1 ryanodine receptor (RyR1) indirectly affects FKBP12/RyR1 interaction causing, on the one hand, an increase in RyR1 channel gating and, on the other hand, a weakening of the DHPRα_1S/RyR1 orthograde signaling. Dysregulation of RyR1 activity of Triadin-null cells leads to enhanced SR Ca²⁺ leakage and subsequent reduction in SR Ca²⁺ content. In addition, lack of Triadin expression activates Ca²⁺ entry pathways that are both store-dependent and store-independent (sensitive to TRPC/Orai-1 inhibitors). Ca²⁺ entry and SR Ca²⁺ leakage could contribute independently to elevate myoplasmic [Ca²⁺]_rest.