Localization and Functional Analysis of Bestrophin

Abstract

Best Macular Dystrophy (BMD) is an inherited autosomal dominant disorder that exhibits symptoms and histopathology reminiscent of age-related macular degeneration (AMD) the leading cause of blindness in the western world. The vitelliform macular dystrophy 2 gene (VMD2), mutated in BMD, encodes a previously unknown protein named bestrophin. Bestrophin is predicted to be a transmembrane protein with 4 membrane spanning alpha helical domains. On the basis of northern blot and in situ hybridization, bestrophin was predicted to be uniquely expressed in the retinal pigment epithelium (RPE). Using bestrophin specific antibodies, we have confirmed the RPE specific localization of bestrophin in the eye, and determined that bestrophin is a basolateral plasma membrane protein. Here we attempt to combine our existing knowledge on structure, cellular localization, and the clinical consequences of mutations of bestrophin, in order to gain insights into its possible function in retina.