Evolutionary origins of retinoid active short-chain dehydrogenases/reductases of SDR16C family. (5th June 2015)

• Record Type: Journal Article
• Authors: Belyaeva, Olga V.; Chang, Chenbei; Berlett, Michael C.; Kedishvili, Natalia Y.
• Is Part Of: Chemico-biological interactions. Volume 234(2015)
• Page Start: 135
• Page End: 143
• Publication Date: 2015-06-05
• Subjects: Short chain dehydrogenases/reductases -- Evolution -- Retinoic acid; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2014.10.026
• Languages: English
• ISSNs: 0009-2797

Abstract

Highlights: Homologs of retinoid-active enzymes of SDR16C family exist in invertebrates. Ascidian and sea urchin SDR16C enzymes are expressed during embryonic development. Ascidian and sea urchin enzymes oxidize retinol when expressed in cells. Abstract: Vertebrate enzymes that belong to the 16C family of short-chain dehydrogenases/reductases (SDR16C) were shown to play an essential role in the control of retinoic acid (RA) levels during development. To trace the evolution of enzymatic function of SDR16C family, and to examine the origins of the pathway for RA biosynthesis from vitamin A, we identified putative SDR16C enzymes through the extensive search of available genome sequencing data in a subset of species representing major metazoan phyla. The phylogenetic analysis revealed that enzymes from protostome, non-chordate deuterostome and invertebrate chordate species are found in three clades of SDR16C family containing retinoid active enzymes, which are retinol dehydrogenase 10 (RDH10), retinol dehydrogenases E2 (RDHE2) and RDHE2-similar, and dehydrogenase reductase (SDR family) member 3 (DHRS3). For the initial functional analysis, we cloned RDH10- and RDHE2-related enzymes from the early developmental stages of a non-chordate deuterostome, green sea urchin Lytechinus variegatus, and an invertebrate chordate, sea squirt Ciona intestinalis . In situ hybridization revealed that these proteins are expressed in a pattern relevant to development, while assays performed on proteins expressed in mammalian cell culture showed that they possess retinol-oxidizing activity as their vertebrate homologs. The existence of invertebrate homologs of DHRS3 was inferred from the analysis of phylogeny and cofactor-binding residues characteristic of preference for NADP(H). The presence of invertebrate homologs in the DHRS3 group of SDR16C is interesting in light of the complex mutually activating interaction, which we have recently described for human RDH10 and DHRS3 enzymes. Further functional analysis of these homologs will establish whether this interaction evolved to control retinoid homeostasis only in vertebrates, or is also conserved in pre-vertebrates.