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

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.

SUBMITTER: Kim H

PROVIDER: S-EPMC6957751 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Kim Hyunsoo H Walsh Matthew C MC Yu Jiyeon J Laskoski Paul P Takigawa Kei K Takegahara Noriko N Choi Yongwon Y

FEBS letters 20190831 1

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. MEP5 ...[more]

PMID: 31432503

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