Intracellular localization and membrane topology of 11-cis retinol dehydrogenase in the retinal pigment epithelium suggest a compartmentalized synthesis of 11-cis retinaldehyde

11-cis retinol dehydrogenase (EC 1.1.1.105) catalyses the last step in the biosynthetic pathway generating 11-cis retinaldehyde, the common chromophore of all visual pigments in higher animals. The enzyme is abundantly expressed in retinal pigment epithelium of the eye and is a member of the short chain dehydrogenase/reductase superfamily. In this work we demonstrate that a majority of 11-cis retinol dehydrogenase is associated with the smooth ER in retinal pigment epithelial cells and that the enzyme is an integral membrane protein, anchored to membranes by two hydrophobic peptide segments. The catalytic domain of the enzyme is confined to a lumenal compartment and is not present on the cytosolic aspect of membranes. Thus, the subcellular localization and the membrane topology of 11-cis retinol dehydrogenase suggest that generation of 11-cis retinaldehyde is a compartmentalized process.