Identification of FAM173B as a protein methyltransferase promoting chronic pain

Hanneke L D M Willemen, Annemieke Kavelaars, Judith Prado, Mirjam Maas, Sabine Versteeg, Lara J J Nellissen, Jeshua Tromp, Rafael Gonzalez Cano, Wenjun Zhou, Magnus E Jakobsson, Jędrzej Małecki, George Posthuma, Abdella M Habib, Cobi J Heijnen, Pål Ø Falnes, Niels Eijkelkamp

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic pain is a debilitating problem, and insights in the neurobiology of chronic pain are needed for the development of novel pain therapies. A genome-wide association study implicated the 5p15.2 region in chronic widespread pain. This region includes the coding region for FAM173B, a functionally uncharacterized protein. We demonstrate here that FAM173B is a mitochondrial lysine methyltransferase that promotes chronic pain. Knockdown and sensory neuron overexpression strategies showed that FAM173B is involved in persistent inflammatory and neuropathic pain via a pathway dependent on its methyltransferase activity. FAM173B methyltransferase activity in sensory neurons hyperpolarized mitochondria and promoted macrophage/microglia activation through a reactive oxygen species-dependent pathway. In summary, we uncover a role for methyltransferase activity of FAM173B in the neurobiology of pain. These results also highlight FAM173B methyltransferase activity as a potential therapeutic target to treat debilitating chronic pain conditions.

Original languageEnglish
Pages (from-to)e2003452
JournalPLoS Biology
Volume16
Issue number2
DOIs
Publication statusPublished - 2018 Feb
Externally publishedYes

Subject classification (UKÄ)

  • Biochemistry and Molecular Biology

Free keywords

  • Animals
  • Chromosomes, Human, Pair 5
  • Chronic Pain/enzymology
  • Female
  • Gene Knockdown Techniques
  • Genome-Wide Association Study
  • HEK293 Cells
  • Histone-Lysine N-Methyltransferase/genetics
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Microglia/metabolism
  • Polymorphism, Single Nucleotide
  • Reactive Oxygen Species/metabolism

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