Cell signalling and vitamin A
Cell proliferation, differentiation and death are controlled by different transcription factors including the non-steroid nuclear receptors (nsNR). RA is the active metabolite of vitamin A, and retinoic acid receptors (RARs) belong to the nsNR family. RA binds to heterodimers of RARs and retinoid X receptors, also called rexinoid receptors (RXRs). These bind to RA response elements found in the regulatory regions of the target genes. It is important to note that heterodimerisation with RXR is not the only pathway for RAR function. In vitro data show that RARs can act via non-canonical signalling pathways independently of RXR. The EU-funded INVIVO_RA_NONCANON (Non-canonical signalling pathways relayed by retinoic acid affecting germ cell differentiation) project wanted to confirm the existence of such pathways and characterise them, using the seminiferous epithelium of the testis as a model system. Researchers developed working hypotheses, which integrated data about genes differentially expressed in RA-deficient contexts with analysis of datasets identifying RAR binding sites. Experimental results confirmed that in the supporting cells of the seminiferous epithelium, the Sertoli cells, RAR acts independently of RXR to control RA-target genes. In the attempt to find the specific non-canonical pathway, a secreted glycoprotein was identified. This protein acts as a downstream effector of RA, enabling germ cell differentiation toward meiosis. Project developments have established the foundation for further investigation of the role of non-canonical RA signalling in gene expression regulation.
Keywords
Vitamin A, retinoic acid, retinoic acid receptor, rexinoid receptor, INVIVO_RA_NONCANON
