Methylosome protein 50 associates with the purinergic receptor P2X5 and is involved in osteoclast maturation

FEBS Lett. 2020 Jan;594(1):144-152. doi: 10.1002/1873-3468.13581. Epub 2019 Aug 31.


Purinergic signaling plays important roles in bone. P2X5, a member of ligand-gated ion channel receptors, has been demonstrated to regulate osteoclast maturation. However, the molecular mechanism of P2X5-mediated osteoclast regulation remains unclear. Here, we identified methylosome protein 50 (MEP50), a critical cofactor of the protein arginine methyltransferase 5 (PRMT5), as a P2X5-associating molecule. RNAi-mediated knockdown of MEP50 results in decreased formation of mature osteoclasts. MEP50 associates with P2X5, and this association requires the C-terminal intracellular region of P2X5. Additionally, impaired maturation of P2X5-deficient osteoclasts could be restored by transduction of full-length P2X5, but not a C-terminal deletion mutant of P2X5. These results indicate that P2X5 associates with MEP50 and suggest a link between the PRMT5 complex and P2X5 signaling in osteoclast maturation.

Keywords: MEP50; P2X5; PRMT5; RNAi-mediated knockdown; maturation; methylosome; osteoclast.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Cell Differentiation*
  • HEK293 Cells
  • Humans
  • Mice
  • Osteoclasts / cytology
  • Osteoclasts / metabolism*
  • Protein Binding
  • Protein-Arginine N-Methyltransferases / metabolism
  • Receptors, Purinergic P2X5 / chemistry
  • Receptors, Purinergic P2X5 / metabolism*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Receptors, Purinergic P2X5
  • Transcription Factors
  • WDR77 protein, mouse
  • Prmt5 protein, mouse
  • Protein-Arginine N-Methyltransferases