Fig. 1: Localization of ABCA4 in photoreceptor rod outer segments and its role in the visual cycle.

a Schematic showing part of a rod outer segment with a stack of disc membrane surrounded by a plasma membrane. ABCA4 is located along the rim and incisures of the disc membrane. b Reversible formation of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from all-trans retinal (ATR) and phosphatidylethanolamine (PE). c Diagram showing the role of ABCA4 in the transport of N-Ret-PE across the disc membrane. Excess 11-cis-retinal (11-cis-ral) not required for the regeneration of rhodopsin reversibly reacts to PE to produce N-Ret-PE (cis). ABCA4 flips N-Ret-PE (cis) from the lumen side to the cytoplasmic side of the disc membrane. Chemical isomerization converts N-Ret-PE (cis) to its trans isomer. Dissociation of N-ret-PE (trans) to ATR and PE enables ATR to be reduced to all-trans retinol (all-trans-rol) by retinol dehydrogenase 8 (RDH8) for entry into the visual cycle. ATR produced by photobleaching of rhodopsin reversibly reacts with PE to form N-Ret-PE (trans) which is flipped to the cytoplasmic leaflet by ABCA4. After dissociation, ATR is reduced to all-trans retinol by RDH8 for entry into the visual cycle.