2. Academic Validation
  3. Identification of FAM173B as a protein methyltransferase promoting chronic pain

Identification of FAM173B as a protein methyltransferase promoting chronic pain

  • PLoS Biol. 2018 Feb 14;16(2):e2003452. doi: 10.1371/journal.pbio.2003452.
Hanneke L D M Willemen 1,  Annemieke Kavelaars 2,  Judith Prado 3,  Mirjam Maas 1,  Sabine Versteeg 1,  Lara J J Nellissen 1,  Jeshua Tromp 1,  Rafael Gonzalez Cano 1 4,  Wenjun Zhou 2,  Magnus E Jakobsson 5,  Jędrzej Małecki 5,  George Posthuma 6,  Abdella M Habib 7 8,  Cobi J Heijnen 2,  Pål Ø Falnes 5,  Niels Eijkelkamp 1 3
Affiliations

Affiliations

  • 1 Laboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • 2 Laboratory of Neuroimmunology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
  • 3 Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • 4 Department of Pharmacology and Institute of Neuroscience, University of Granada, Granada, Spain.
  • 5 Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
  • 6 Department of Cell Biology and Institute of Biomembranes, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
  • 7 Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London, United Kingdom.
  • 8 College of Medicine, Member of Qatar Health, Qatar University, Doha, Qatar.
PMID: 29444090 DOI: 10.1371/journal.pbio.2003452
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.

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