Identification of the Functional Role of Dysferlin
Although it proposed that dysferlin plays a key role in rapid calcium-mediated membrane resealing, very little is known regarding how it performs this role. The seven putative C2 domains within dysferlin suggest a high degree of modulation by intracellular calcium, likely mediating interactions central to its role in membrane repair. We are studying the cellular biology of dysferlin in cultured muscle cells, and have developed two membrane repair assays to study the functional role of dysferlin in membrane repair. We are particularly interested in determining the molecular roles of dysferlin C2 domains, and have developed a large panel of dysferlin expression constructs with targeted deletion or mutation of different domains.
To try and define a day-in-the-life of dysferlin, we are using our dysferlin deletion constructs and patient missense mutants to illuminate dysferlin behaviour gone awry, as well as comparative studies of other ferlins. In this way, we hope to identify roles that are specific to dysferlin, and may therefore be important in the pathogenesis of dysferlinopathy.