A model for transport of membrane-associated phototransduction polypeptides in rod and cone photoreceptor inner segments.

We discuss putative mechanisms of membrane protein transport in photoreceptors based on Pde6d and Gucy2e/Gucy2f knockout mice. Knockout of the Pde6d gene encoding PrBP/delta, a prenyl binding protein present in the retina at relatively high levels, was shown to impair transport of G-protein coupled receptor kinase 1 (GRK1) and cone phosphodiesterase alpha' subunit (PDE6alpha') to the rod and cone outer segments. Other prenylated proteins are minimally affected, suggesting some specificity of interaction. Knockout of the Gucy2e gene encoding guanylate cyclase 1 (GC1) disrupted transport of G-protein coupled receptor kinase 1 (GRK1), cone PDE6alpha', cone transducin alpha and gamma subunits (cTalpha and cTgamma) to the cone outer segments, while a GC1/GC2 double knockout prevented transport of rod PDE6, but not transducin, GRK1, or rhodopsin, to the rod outer segments. These knockout phenotypes suggest that PrBP/delta functions in extracting prenylated proteins from the endoplasmic reticulum (ER) where they dock after prenylation, and that GC-bearing membranes may co-transport peripheral membrane proteins in vesicles. We conclude that distinct pathways have evolved in rods and cones for transport of integral and peripherally membrane-associated proteins.