Molecular Chaperones for Missense Dysferlin

Simone Spuler, MD

Charite, University Medicine (Berlin, Germany)

Dr. Simone Spuler is a neurologist and full professor for myology at the Experimental and Clinical Research Center of the Charite, University Medicine Berlin and the Max-Delbruck Center of Molecular Medicine, Berlin, Germany.

Past Projects

Objective: 
Prevent the misfolding and aggregation of mutant dysferlins.

Many patients with missense mutations in the dysferlin gene show no detectable dysferlin in muscle biopsies, even though their genetic mutations suggest that they should be able to produce a partially-functional dysferlin protein. For several missense mutations in dysferlin it has convincingly been shown by us and others that amino acid exchanges lead to protein misfolding and subsequently to aggregation of dysferlin in the endoplasmic reticulum. ERADI and ERADII are involved in the degradation process of trapped dysferlin. This project redirects mutated dysferlin trapped in the ER to the plasma membrane of myotubes and muscle fibers with short peptides derived from dysferlin itself. We have been able to demonstrate that the presence of TAT-labeled dysferlin peptides within the myotube results in recovery of dysferlin on the sarcolemma.