Dissection of the pathway required for generation of vitamin A and for Drosophila phototransduction

Abstract

Dietary carotenoids are precursors for the production of retinoids, which participate in many essential processes, including the formation of the photopigment rhodopsin. Despite the importance of conversion of carotenoids to vitamin A (all-trans-retinol), many questions remain concerning the mechanisms that promote this process, including the uptake of carotenoids. We use the Drosophila visual system as a genetic model to study retinoid formation from β-carotene. In a screen for mutations that affect the biosynthesis of rhodopsin, we identified a class B scavenger receptor, SANTA MARIA. We demonstrate that SANTA MARIA functions upstream of vitamin A formation in neurons and glia, which are outside of the retina. The protein is coexpressed and functionally coupled with the β, β-carotene-15, 15′-monooxygenase, NINAB, which converts β-carotene to all-trans-retinal. Another class B scavenger receptor, NINAD, functions upstream of SANTA MARIA in the uptake of carotenoids, enabling us to propose a pathway involving multiple extraretinal cell types and proteins essential for the formation of rhodopsin.

SNMP is a signaling component required for pheromone sensitivity in Drosophila

“…CD36 knockout mice are defective for uptake of fatty acids into muscle and heart, and macrophages from these lines fail to take up oxidized cholesterol (18,(26)(27)(28). In Drosophila, other CD36 homologs are important for recognition and removal of dead cells (29) and bacteria (30), and absorption of vitamin A from the gut (31, 32) and transfer into the retina (33). In vertebrates, CD36 proteins function as receptors and signal transduction molecules.…”

Phototransduction and retinal degeneration in Drosophila

“…5) [71,75,76]. Two other genes, ninaD [71,77] and santa maria (scavenger receptor acting in neural tissue and majority of rhodopsin is absent) [78] encode proteins related to mammalian class B scavenger receptors. As such, NINAD and SANTA MARIA may mediate the transport of β-carotene into cells [77][78][79].…”

“…The question arises as to the identity of the scavenger receptor that may function in concert with NINAB. Although NINAD has been suggested to play such a role [80], the different expression patterns of ninaB and ninaD make this hypothesis unlikely [78]. Rather, santa maria and ninaB are expressed and function in the same extraretinal glia and neuronal cells in fly heads.…”

“…Rather, santa maria and ninaB are expressed and function in the same extraretinal glia and neuronal cells in fly heads. Therefore, SANTA MARIA appears to mediate uptake of carotenoids from circulation into both neuronal and glia cells, thereby providing the substrates for processing of carotenoids to retinal by NINAB [78]. NINAD appears to function in the uptake of carotenoids primarily in the midgut [78].…”

“…Instead of being metabolized in the midgut, β-carotene is delivered to neurons and glia through circulation and taken up into these cells via the SANTA MARIA scavenger receptor. The NINAB BCO subsequently functions in the same neurons and glia as SANTA MARIA in the centric cleavage of β-carotene to retinal [78]. The all-trans-retinol is then transferred to the retinal pigment cells, where it is converted into the chromophore, through a process involving the PINTA retinoid binding protein and the NINAG oxidoreductase [81,82].…”