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Identification of FAM173B as a protein methyltransferase promoting chronic pain

Willemen, Hanneke L D M ; Kavelaars, Annemieke ; Prado, Judith ; Maas, Mirjam ; Versteeg, Sabine ; Nellissen, Lara J J ; Tromp, Jeshua ; Gonzalez Cano, Rafael ; Zhou, Wenjun and Jakobsson, Magnus E LU , et al. (2018) In PLoS Biology 16(2). p.2003452-2003452
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... (More)

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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Contribution to journal
publication status
published
subject
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
in
PLoS Biology
volume
16
issue
2
pages
2003452 - 2003452
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:29444090
  • scopus:85043709310
ISSN
1545-7885
DOI
10.1371/journal.pbio.2003452
language
English
LU publication?
no
id
dd2c5fb4-27c9-4c3e-87e9-99f70aa8b2c1
date added to LUP
2020-01-13 08:52:31
date last changed
2024-03-20 03:40:11
@article{dd2c5fb4-27c9-4c3e-87e9-99f70aa8b2c1,
  abstract     = {{<p>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.</p>}},
  author       = {{Willemen, Hanneke L D M and Kavelaars, Annemieke and Prado, Judith and Maas, Mirjam and Versteeg, Sabine and Nellissen, Lara J J and Tromp, Jeshua and Gonzalez Cano, Rafael and Zhou, Wenjun and Jakobsson, Magnus E and Małecki, Jędrzej and Posthuma, George and Habib, Abdella M and Heijnen, Cobi J and Falnes, Pål Ø and Eijkelkamp, Niels}},
  issn         = {{1545-7885}},
  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}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{2003452--2003452}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Biology}},
  title        = {{Identification of FAM173B as a protein methyltransferase promoting chronic pain}},
  url          = {{http://dx.doi.org/10.1371/journal.pbio.2003452}},
  doi          = {{10.1371/journal.pbio.2003452}},
  volume       = {{16}},
  year         = {{2018}},
}