Rapid 1α,25(OH)2D3 membrane-mediated activation of Ca 2+/calmodulin-dependent protein kinase II in growth plate chondrocytes requires Pdia3, PLAA and caveolae

Maryam Doroudi, Barbara D. Boyan, Zvi Schwartz

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


1α,25-Dihydroxy vitamin D3 [1α,25(OH)2D3] regulates growth zone chondrocytes (GC) via classical steroid hormone receptor-mediated gene transcription and by initiating rapid membrane-mediated signaling pathways. 1α,25(OH)2D3 initiates its membrane effects via its specific membrane-associated receptor (Pdia3) in caveolae. 1α,25(OH)2D3 binding to Pdia3 leads to phospholipase-A2 (PLA2)-activating protein (PLAA) activation, stimulating PLA2, resulting in prostaglandin E2 (PGE2) release and protein kinase C activation. Recently, we reported that 1α,25(OH)2D3 rapidly activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) in GC cells. However, the roles of Pdia3, PLAA and caveolae in 1α,25(OH)2D3- dependent rapid activation of CaMKII are not clear. The aim of the present study was to evaluate the roles of Pdia3, PLAA and caveolae in 1α,25(OH)2D3 membrane-stimulated CaMKII activation. Pre-treating chondrocytes from the growth zone of the rat costochondral cartilage with antibodies against PLAA or Pdia3 blocked activation of CaMKII by 1α,25(OH)2D3. PLAA peptide rapidly activated CaMKII in GC cells. Caveolae disruption abolished CaMKII activation in response to 1α,25(OH)2D3 or PLAA peptide treatment. Immunoprecipitation studies showed increased CaM binding to PLAA in response to 1α,25(OH)2D3. The results indicated that Pdia3, PLAA and caveolae are required for rapid 1α,25(OH)2D3 membrane-mediated activation of CaMKII. 1α,25(OH)2D3 signaling via Pdia3 receptor triggered the interaction between PLAA and CaM suggesting that CaM may play a major role linking PLAA to CaMKII in membrane-mediated actions of 1α,25(OH)2D3.

Original languageEnglish (US)
Pages (from-to)125-128
Number of pages4
JournalConnective Tissue Research
Issue numberSUPPL. 1
StatePublished - 2014


  • Caveolae
  • Non-genomic actions
  • Phospholipase A2 activating protein
  • Protein disulfide isomerase A3
  • Rapid actions
  • Secosteroid hormone

ASJC Scopus subject areas

  • Rheumatology
  • Biochemistry
  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology


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