Trichoplax adhaerens reveals a network of nuclear receptors sensitive to 9- cis-retinoic acid at the base of metazoan evolution

PeerJ. 2017 Sep 29:5:e3789. doi: 10.7717/peerj.3789. eCollection 2017.


Trichoplax adhaerens, the only known species of Placozoa is likely to be closely related to an early metazoan that preceded branching of Cnidaria and Bilateria. This animal species is surprisingly well adapted to free life in the World Ocean inhabiting tidal costal zones of oceans and seas with warm to moderate temperatures and shallow waters. The genome of T. adhaerens (sp. Grell) includes four nuclear receptors, namely orthologue of RXR (NR2B), HNF4 (NR2A), COUP-TF (NR2F) and ERR (NR3B) that show a high degree of similarity with human orthologues. In the case of RXR, the sequence identity to human RXR alpha reaches 81% in the DNA binding domain and 70% in the ligand binding domain. We show that T. adhaerens RXR (TaRXR) binds 9-cis retinoic acid (9-cis-RA) with high affinity, as well as high specificity and that exposure of T. adhaerens to 9-cis-RA regulates the expression of the putative T. adhaerens orthologue of vertebrate L-malate-NADP+ oxidoreductase (EC which in vertebrates is regulated by a heterodimer of RXR and thyroid hormone receptor. Treatment by 9-cis-RA alters the relative expression profile of T. adhaerens nuclear receptors, suggesting the existence of natural ligands. Keeping with this, algal food composition has a profound effect on T. adhaerens growth and appearance. We show that nanomolar concentrations of 9-cis-RA interfere with T. adhaerens growth response to specific algal food and causes growth arrest. Our results uncover an endocrine-like network of nuclear receptors sensitive to 9-cis-RA in T. adhaerens and support the existence of a ligand-sensitive network of nuclear receptors at the base of metazoan evolution.

Keywords: 9-cis retinoic acid; COUP; ERR; Food; HNF4; Nuclear receptor; RXR; Trichoplax adhaerens.

Grants and funding

The main funding sources were: 1/the European Regional Development Fund “BIOCEV—Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University in Vestec” (CZ.1.05/1.1.00/02.0109) (The Start-Up Grant to the group Structure and Function of Cells in Their Normal State and in Pathology—Integrative Biology and Pathology (5.1.10)); 2/ The grant PRVOUK-P27/LF1/1 from the Charles University; 3/The grants SVV 260377/2017, SVV260257/2016, SVV260149/2015 and SVV 260023/2014 from the Charles University. This work was supported by the research project PRVOUK—Oncology P27, awarded by Charles University in Prague and by the project OPPK No. CZ.2.16/3.1.00/24024, awarded by European Fund for Regional Development (Prague & EU—We invest for your future). PROGRES Q26/LF1. This work was also supported by the Ministry of Education, Youth and Sports of CR within the LQ1604 National Sustainability Program II (Project BIOCEV-FAR) and by the project “BIOCEV” (CZ.1.05/1.1.00/02.0109). The work of Radek Kaňa was further supported by GACR 16-10088S and by the institutional projects Algatech Plus (MSMT LO1416) and Algamic (CZ 1.05/2.1.00/19.0392) provided by the Ministry of Education, Youth and Sports of the Czech Republic. For getting the project started Bernd Schierwater received support from the German Science Foundation (DEG Schi 277/27-1 and Schi 277/29-1). Authors received monetary support of the work reported in this publication from MediCentrum Praha. Zdenek Kostrouch and Marta Kostrouchová contributed with personal funds to this work. The funders (except authors) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.