Figure 7. Alteration of triad components and proteins regulating membrane trafficking.

Immunolocalization on longitudinal and transversal sections from patients and affected dogs revealed an abnormal pattern of the junctional sarcoplasmic calcium channel RYR1, the T-tubule marker DHPR and the longitudinal sarcoplasmic calcium pump SERCA1. Especially RYR1 was found to accumulate around internalized nuclei. Intracellular dysferlin signals were detected in patients and affected dogs, but not in the age-matched controls. Labeling of the sarcolemmal markers caveolin 3 and dystrophin demonstrated prominent lobulation and deep indentations of the plasma membrane in patients and affected dogs on transversal and longitudinal sections (arrows).