Membrane receptors for vitamin D metabolites.
Membrane-initiated signaling by steroid hormones is now widely accepted. Current debate is centered upon which protein moieties act as membrane-associated receptors. In this review, we consider evidence for the classical vitamin D receptor (VDR) in this role, as well as the more recently identified 1,25D3-MARRS (membrane-associated, rapid response steroid binding) receptor, also known as ERp57/GRp58. The structure of the 1,25D3-MARRS receptor is discussed, with emphasis on two thioredoxin domains that promote dimerization and ligand binding. We then summarize recent studies on a 24,25(OH)2D3 binding protein--catalase--and how ligand-induced decreases in enzymatic activity produce increased reactive oxygen species that target both the 1,25D3-MARRS receptor--but not the VDR--and the protein kinase C signaling pathway. Finally, we briefly discuss the available literature suggesting that the metabolite 25(OH)D3 may also be biologically active.
Khanal
R
R
Department of Nutrition and Food Sciences and the Center for Integrated BioSystems, Utah State University, Logan, UT 84322-8700, USA.
Nemere
Ilka
I
D015650:24,25-Dihydroxyvitamin D 3 / Q000378:metabolism*; D000818:Animals; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism*
D008565:Membrane Proteins; D018167:Receptors, Calcitriol; D014807:Vitamin D; D015650:24,25-Dihydroxyvitamin D 3; D019704:Protein Disulfide-Isomerases