Plasma membrane Pdia3 and VDR interact to elicit rapid responses to 1α,25(OH)2D3

Jiaxuan Chen, Maryam Doroudi, Jeffery Cheung, Ashley L. Grozier, Zvi Schwartz, Barbara D. Boyan

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) regulates osteoblasts through genomic and rapid membrane-mediated responses. Here we examined the interaction of protein disulfide isomerase family A, member 3 (Pdia3) and the traditional vitamin D receptor (VDR) in plasma membrane-associated responses to 1α,25(OH)2D3. We found that Pdia3 co-localized with VDR and the caveolae scaffolding protein, caveolin-1 on the surface of MC3T3-E1 osteoblasts. Immunoprecipitation showed that both Pdia3 and VDR interacted with caveolin-1. Pdia3 further interacted with phospholipase A2 activating protein (PLAA), whereas VDR interacted with c-Src. 1α,25(OH)2D3 changed the interactions and transport of the two receptors and rapidly activated phospholipase A2 (PLA2) and c-Src. Silencing either receptor or caveolin-1 inhibited both PLA2 and c-Src, indicating that the two receptors function interdependently. These two receptor dependent rapid responses to 1α,25(OH)2D3 regulated gene expression, proliferation and apoptosis of MC3T3-E1 cells. These data demonstrate the importance of both receptors and caveolin-1 in mediating membrane responses to 1α,25(OH)2D3 and subsequently regulating osteoblast biology.

Original languageEnglish (US)
Pages (from-to)2362-2373
Number of pages12
JournalCellular Signalling
Volume25
Issue number12
DOIs
StatePublished - Jan 1 2013

Keywords

  • Caveolin-1
  • MC3T3-E1 cells
  • Pdia3
  • Rapid responses
  • VDR

ASJC Scopus subject areas

  • Cell Biology

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    Chen, J., Doroudi, M., Cheung, J., Grozier, A. L., Schwartz, Z., & Boyan, B. D. (2013). Plasma membrane Pdia3 and VDR interact to elicit rapid responses to 1α,25(OH)2D3. Cellular Signalling, 25(12), 2362-2373. https://doi.org/10.1016/j.cellsig.2013.07.020