Downregulation of a unique photoreceptor protein correlates with improper outer segment assembly.

A unique photoreceptor protein has been characterized. This protein, termed XAP-1 antigen, is expressed by photoreceptors exclusively under conditions in which the outer segment membranes are properly assembled. When the retinal pigment epithelium is adherent to the underlying neural retina, the XAP-1 antigen is localized to the plasma membrane that surrounds the inner and outer segments in the areas juxtaposed to the subretinal space. A similar labeling pattern is detected in retinal pigment epithelium-deprived retinas in which assembly of nascent outer segments is supported by lactose. In retinas that undergo degeneration subsequent to the removal of the retinal pigment epithelium, the expression of this protein is completely downregulated. Immunohistochemical analyses and subcellular fractionation along with Western blot analysis, indicate that the XAP-1 antigen is a membrane-associated soluble protein. Mass spectrometric analysis indicates that the XAP-1 antigen shares homology via 12 tryptic peptide masses with the gamma-crystallin (lens structural protein) subclasses, although it does not immunolocalize to the same ocular structures as reported for the gamma-crystallins. We propose that XAP-1 antigen is a unique protein that is expressed extensively by healthy photoreceptor cells; the expression of the XAP-1 antigen exclusively by photoreceptors with organized outer segments suggests that this protein may play a critical role in outer segment assembly. Copyright 2002 Wiley-Liss, Inc.