Retinol Metabolism in the Mollusk Osilinus lineatus Indicates an Ancient Origin for Retinyl Ester Storage Capacity

Abstract

Although retinoids have been reported to be present and active in vertebrates and invertebrates, the presence of mechanisms for retinoid storage in the form of retinyl esters, a key feature to maintain whole-organism retinoid homeostasis, have been considered to date a vertebrate innovation. Here we demonstrate for the first time the presence of retinol and retinyl esters in an invertebrate lophotrochozoan species, the gastropod mollusk Osilinus lineatus. Furthermore, through a pharmacological approach consisting of intramuscular injections of different retinoid precursors, we also demonstrate that the retinol esterification pathway is active in vivo in this species. Interestingly, retinol and retinyl esters were only detected in males, suggesting a gender-specific role for these compounds in the testis. Females, although lacking detectable levels of retinol or retinyl esters, also have the biochemical capacity to esterify retinol, but at a lower rate than males. The occurrence of retinyl ester storage capacity, together with the presence in males and females of active retinoids, i.e., retinoic acid isomers, indicates that O. lineatus has a well developed retinoid system. Hence, the present data strongly suggest that the capacity to maintain retinoid homeostasis has arisen earlier in Bilateria evolution than previously thought.

Alternative Splicing Profile and Sex-Preferential Gene Expression in the Female and Male Pacific Abalone Haliotis discus hannai

“…Regarding the generally identifed functions of cubilin, we may suggest its putative diversified roles based on previous observations from mollusks including Haliotis sp.. Vitamin D metabolism is curcial in normal growth and shell mineralization of H. discus hannai [31,32]. Mollusks would have conserved and active retinol metabolism, as high retinyl ester storage capacity was observed with active retinoids in gastropod lineages [33,34]. Transcobalamin is a carrier protein which directly binds to cobalamin (vitamin B12).…”

Expression of a retinoic acid receptor (RAR)-like protein in the embryonic and adult nervous system of a protostome species

“…Retinoid signaling has however, been conserved in protostome lophotrochozoans; both the annelid C. capitata and the mollusc L. gigantea have the "complete RA-gene toolkit" in their genomes (Albalat and Canestro, 2009). Recently, Gesto et al (2012) provided evidence for retinoid storage in the form of retinyl esters, as well as retinaldehyde conversion into retinoic acid in the gastropod mollusc O.lineatus. The in silico evidence for the presence of RARs in various protostome species (Albalat and Canestro, 2009) is strengthened by the discovery of other liganded nuclear receptors (thought to be chordate-specific) in lophotrochozoans (Thornton et al, 2003;Bertrand et al, 2004).…”

“…Many aspects of retinoid signaling, such as retinoic acid synthesis, storage, and particularly signaling via RARs were originally believed to be a vertebrate innovation, yet mounting evidence has now pushed these back to the common ancestor of the Bilateria, the Urbilateria (Simoes‐Costa et al, ; Albalat and Canestro, ; Gesto et al, ). However, some retinoid signaling genes appear to have been lost in the lineage to ecdysozoans, particularly insects and nematodes.…”

Molecular Basis for Vitamin A Uptake and Storage in Vertebrates

“…Although certain retinoid metabolites characteristic for the metabolic pathways involved in maintaining retinoid homeostasis can be found in early metazoans, the key genes that encode LRAT, RBP, and STRA6 are absent in invertebrate genes [98,99]. The reported presence of REs in tissues of sponges and two gastropods species can instead be attributed to the activity of DGAT1 orthologues [100,101,102]. Moreover, the absence of the capability to recruit REs in several other invertebrate lineages strongly suggests lack of a coherent mechanism for vitamin A storage [103].…”