The ERp57/GRp58/1,25D3-MARRS receptor: multiple functional roles in diverse cell systems.
ERp57/GRp58 is a thiol-protein disulphide oxidoreductase and has been studied in many clinically relevant systems, both as a chaperone protein and as a membrane receptor for the steroid hormone, 1,25(OH)2D3. Our laboratory investigates phenomena associated with rapid, membrane-initiated signaling by steroid hormones synthesized from vitamin D (cholecalciferol). We have recently reported that the cell surface receptor for the metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], which we have termed the 1,25D3-MARRS (Membrane Associated, Rapid Response Steroid binding) receptor, is in fact identical to ERp57/GRp58. Here we review the dynamic role ERp57/GRp58/1,25D3-MARRS receptor plays in a variety of cellular processes. Starting with its structure at the DNA and protein levels, we review the available literature about its role as a chaperone protein, in immune function through the assembly of MHC class I molecules, DNA binding, and its function as the 1,25D3-MARRS receptor. Finally, we present the role it may play in relation to important disease states. While ERp57/GR58/1,25D3-MARRS receptor is a pivotal protein in many cell functions, it has yet to be determined whether-and to what extent-these phenomena are regulated by the vitamin D endocrine system. However, 1,25(OH)2D3 is involved in differentiation of certain cancer cells and in muscle function, and ERp57/1,25D3-MARRS protein has been reported to be involved in such processes. Thus, medicinal chemistry aimed at the 1,25D3-MARRS receptor in lymphocytes, cancer cells, bone, intestinal epithelia, and kidney may add to the current therapeutic regimens for various disease states.
Khanal
R C
RC
Department of Nutrition and Food Sciences, Utah State University, Logan, UT 84322-8700, USA.
Nemere
I
I
D000818:Animals; D002117:Calcitriol / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D005805:Genes, MHC Class I; D006801:Humans; D007109:Immunity / Q000502:physiology; D018832:Molecular Chaperones; D019704:Protein Disulfide-Isomerases / Q000502:physiology*
D018832:Molecular Chaperones; D004247:DNA; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human; D002117:Calcitriol