Dysferlin in the heart

Dysferlinopathies are muscular dystrophies affecting mainly the skeletal muscle. Cardiomyopathies are not regarded to be prominent symptoms in Dysferlin deficiency. However, after publishing our paper on Dysferlin's role in skeletal muscle T-tubule development, we were curious to study the role of Dysferlin in the heart and its potential contribution to cardiac TATS (transverse-axial tubule system) formation. When imaging Dysferlin in single cardiomyocytes isolated from healthy rats and mice, we found the protein localizing to the TATS. And we show that expression of Dysferlin is upregulated during development and regeneration. In Dysferlin-deficient cardiomyocytes, we observed loss of transverse TATS components. When we looked at calcium homeostasis of Dysferlin knockout mouse cardiomyocytes, we found no defect under basal conditions, but induction of stress unmasked abnormalities in calcium handling and arrhythmia susceptibility. So, also in the heart, Dysferlin is needed for maintenance of TATS structure and absence of Dysferlin and the resulting defects in TATS structure lead to abnormal calcium handling and may contribute to cardiac dysfunction in dysferlinopathy patients. More details in our publication with first authors Julia and Kristina. https://pubmed.ncbi.nlm.nih.gov/28104817/

Model of dysferlin function in the heart