Publication Date:
2022-05-25
Description:
Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Journal of Steroid Biochemistry and Molecular Biology 184 (2018): 11-19, doi:10.1016/j.jsbmb.2018.06.014.
Description:
Steroid hormone receptors are important regulators of development and physiology in bilaterian
animals, but the role of steroid signaling in cnidarians has been contentious. Cnidarians produce
steroids, including A-ring aromatic steroids with a side-chain, but these are probably made through
pathways different than the one used by vertebrates to make their A-ring aromatic steroids. Here we
present comparative genomic analyses indicating the presence of a previously undescribed nuclear
receptor family within medusozoan cnidarians, that we propose to call NR3E. This family predates
the diversification of ERR/ER/SR in bilaterians, indicating that the first NR3 evolved in the
common ancestor of the placozoan and cnidarian-bilaterian with lineage-specific loss in the
anthozoans, even though multiple species in this lineage have been shown to produce aromatic
steroids, whose function remain unclear. We discovered serendipitously that a cytoplasmic factor
within epidermal cells of transgenic Hydra vulgaris can trigger the nuclear translocation of
heterologously expressed human ERα. This led us to hypothesize that aromatic steroids may also be
present in the medusozoan cnidarian lineage, which includes Hydra, and may explain the
translocation of human ERα. Docking experiments with paraestrol A, a cnidarian A-ring aromatic
steroid, into the ligand-binding pocket of Hydra NR3E indicates that, if an aromatic steroid is
indeed the true ligand, which remains to be demonstrated, it would bind to the pocket through a
partially distinct mechanism from the manner in which estradiol binds to vertebrate ER.
Description:
KK is supported by grant from Japan Society for the
Promotion of Science (JSPS 17K07420). I.M.L.B and Y.C. acknowledge the support and the use of
resources of the French Infrastructure for Integrated Structural Biology FRISBI ANR-10-INBS-05
and of Instruct-ERIC. AMR was supported by NIH Award R15GM114740. AMT was supported by
an Internal Research and Development Award from the Woods Hole Oceanographic Institution.
Keywords:
A-ring aromatic steroid
;
Aromatization
;
Steroid receptor
;
Cnidarian
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
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