The many different cellular functions of MYO7A in the retina

Mutations in MYO7A (myosin Vila) cause Usher syndrome type 18, a disorder involving profound congenital deafness and progressive blindness. In the retina, most MYO7A is localized in the apical region of the RPE (retinal pigmented epithelial) cells, and a small amount is associated with the ciliary and periciliary membranes of the photoreceptor cells. Its roles appear to be quite varied. Studies with MYO7A-null mice indicate that MYO7A participates in the apical localization of RPE melanosomes and in the removal of phagosomes from the apical RPE for their delivery to lysosomes in the basal RPE. In the first role, MYO7A competes with microtubule motors, but in the second one, it may function co-operatively. An additional role of MYO7A in the RPE is indicated by the requirement for it in the light-dependent translocation of the ER (endoplasmic reticulum)-associated visual cycle enzyme RPE65 and normal functioning of the visual retinoid cycle. In photoreceptor cells lacking MYO7A, opsin accumulates abnormally in the transition zone of the cilium, suggesting that MYO7A functions as a selective barrier for membrane proteins at the distal end of the transition zone. It is likely that the progressive retinal degeneration that occurs in Usher syndrome 16 patients results from a combination of cellular defects in the RPE and photoreceptor cells.