title: A review of 1α,25(OH)2D3 dependent Pdia3 receptor complex components in Wnt5a non-canonical pathway signaling.
abstract: Wnt5a and 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] regulate endochondral ossification. 1α,25(OH)2D3 initiates its calcium-dependent effects via its membrane-associated receptor, protein disulfide isomerase A3 (Pdia3). 1α,25(OH)2D3 binding to Pdia3 triggers the interaction between Pdia3 and phospholipase A2 (PLA2)-activating protein (PLAA), resulting in downstream activation of calcium/calmodulin-dependent protein kinase II (CaMKII), PLA2, and protein kinase C (PKC). Wnt5a initiates its calcium-dependent effects via binding its receptors Frizzled2 (FZD2) and Frizzled5 (FZD5) and receptor tyrosine kinase-like orphan receptor 2 (ROR2), activating intracellular calcium release and stimulating PKC and CaMKII. Recent efforts to determine the inter-relation between Wnt5a and 1α,25(OH)2D3 signaling pathways have demonstrated that Wnt5a signals through a CaMKII/PLA2/PGE2/PKC cascade in chondrocytes and osteoblasts in which the components of the Pdia3 receptor complex were required. Furthermore, ROR2, but not FZD2 or FZD5, was required to mediate the calcium-dependent actions of 1α,25(OH)2D3. This review provides evidence that 1α,25(OH)2D3 and Wnt5a mediate their calcium-dependent pathways via similar receptor components and proposes that these pathways may interact since they are competing for the same receptor complex components.
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Doroudi
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Olivares-Navarrete
authors.affiliation: School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA. Electronic address: bboyan@vcu.edu.
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA; Department of Periodontics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78284, USA.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002460:Cell Line; D051157:Frizzled Receptors / Q000378:metabolism; D006801:Humans; D051379:Mice; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: D051157:Frizzled Receptors; C489743:Fzd2 protein, mouse; C403211:Fzd5 protein, mouse; D011506:Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; C055324:phospholipase A2-activating protein; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; D002117:Calcitriol
keywords: 1,25-Dihydroxyvitamin D3; Calmodulin; Phospholipase A2 activating protein; Protein disulfide isomerase A3; Protein kinase C; Wnt5a