Molecular-Functional Comparison of the Dysferlin Membrane Repair Complex with the Otoferlin Synaptic Complex
Genetically-defective dysferlin causes LGMD2B muscular dystrophy and mutated otoferlin causes DFNB9 deafness. Both proteins normally function by forming complexes with other proteins that either repair muscle (dysferlin) or promote hearing through sound-signal transmission (otoferlin). We are investigating the molecular role of dysferlin in muscle, guided by known ferlin interactions in inner ear hair cells, in an examination of the generalized molecular properties of dysferlin across tissues. By using biochemical and molecular-biological binding methods, we are detecting the strongest protein-protein interactions and thus identifying key protein players likely to be part of the dysferlin (and otoferlin) protein complexes that are responsible for membrane repair and fusion. We are also assessing binding properties of particular regions of dysferlin, to provide information on the structure and functions of the protein. Understanding these protein complexes through a comparative approach further guides therapeutic intervention.