EVIDENCE FROM NORMAL AND DEGENERATING PHOTORECEPTORS THAT 2 OUTER SEGMENT INTEGRAL MEMBRANE-PROTEINS HAVE SEPARATE TRANSPORT PATHWAYS

Detachment of the neural retina from the retinal pigment epithelium in duces photoreceptor degeneration. We studied the effects of this degen eration on the localization of two photoreceptor outer segment-specifi c integral membrane proteins, opsin and peripherin/rds, in rod photore ceptors. Results from laser scanning confocal microscopic and electron microscopic immunolocalization demonstrate that these two proteins, n ormally targeted to the newly-forming discs of the outer segments, acc umulate in different sub-cellular compartments during photoreceptor de generation: opsin immunolabeling increases throughout the photorecepto r cell's plasma membrane, while peripherin/rds immunolabeling occurs w ithin cytoplasmic vesicles. The simplest hypothesis to explain our res ults is that these proteins are transported in different post-Golgi tr ansport vesicles and separately inserted into the plasma membrane. Mor e complex mechanisms involve having the two co-transported and then op sin finds its way into the plasma membrane but peripherin/rds does not , remaining behind in vesicles. Alternatively, both insert into the pl asma membrane but peripherin/rds is recycled into cytoplasmic vesicles . We believe the data most strongly supports the first possibility. Al though the transport pathways for these proteins have not been fully c haracterized, the presence of peripherin/rds-positive vesicles adjacen t to the striated rootlet suggests a transport role for this cytoskele tal element.The accumulation of these proteins in photoreceptors with degenerated outer segments may also indicate that their rate of synthe sis has exceeded the combined rates of their incorporation into newly forming outer segment disc membranes and their degradation. The accumu lation may also provide a mechanism for rapid recovery of the outer se gment following retinal reattachment and return of the photoreceptor c ell to an environment favorable to outer segment regeneration. (C) 199 7 Wiley-Liss, Inc.