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Vitamin D receptor(s): In the nucleus but also at membranes?
Author(s) -
Zmijewski Michal A.,
Carlberg Carsten
Publication year - 2020
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.14147
Subject(s) - calcitriol receptor , cytosol , microbiology and biotechnology , vitamin d and neurology , transcriptome , biology , transcription factor , nuclear receptor , vitamin , chemistry , biochemistry , gene , gene expression , enzyme , endocrinology
The genomic actions of the vitamin D are mediated via its biologically most potent metabolite 1α,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) and the transcription factor vitamin D receptor (VDR). Activation of VDR by 1,25(OH) 2 D 3 leads to change in the expression of more 1000 genes in various human tissues. Based on (epi)genome, transcriptome and crystal structure data the molecular details of this nuclear vitamin D signalling pathway are well understood. Vitamin D is known for its role on calcium homeostasis and bone formation, but it also modulates energy metabolism, innate and adaptive immunity as well as cellular growth, differentiation and apoptosis. The observation of rapid, non‐genomic effects of 1,25(OH) 2 D 3 at cellular membranes and in the cytosol initiated the question, whether there are alternative vitamin D‐binding proteins in these cellular compartments. So far, the best candidate is the enzyme PDIA3 (protein disulphide isomerase family A member 3), which is found at various subcellular locations. Furthermore, also VDR seems to play a role in membrane‐based responses to vitamin D. In this viewpoint, we will dispute whether these rapid, non‐genomic pathways are a meaningful addition to the genome‐wide effects of vitamin D.