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

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

Author information

1
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Abstract

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

PMID:
31432503
PMCID:
PMC6957751
[Available on 2021-01-01]
DOI:
10.1002/1873-3468.13581

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