Abstract
Rhodopsin is the light receptor in rod photoreceptor cells of the retina that plays a central role in phototransduction and rod photoreceptor cell health. Rhodopsin mutations are the leading known cause of autosomal dominant retinitis pigmentosa, a retinal degenerative disease. A majority of rhodopsin mutations cause misfolding and aggregation of the apoprotein opsin. The nature of aggregates formed by misfolded rhodopsin mutants and the associated cell toxicity is poorly understood. Misfolding rhodopsin mutants have been characterized biochemically, and categorized as either partial or complete misfolding mutants. This classification is incomplete and does not provide sufficient information to fully understand rhodopsin aggregation, disease pathogenesis, and evaluate therapeutic strategies. To better understand the aggregation of misfolded rhodopsin mutants, a Förster resonance energy transfer assay has been developed to monitor the aggregation of fluorescently tagged mutant rhodopsins expressed in live cells.
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