Identification of FAM173B as a protein methyltransferase promoting chronic pain
(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.
(Less)
- author
- publishing date
- 2018-02
- type
- 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
-
- scopus:85043709310
- pmid:29444090
- 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
- 2024-06-26 09:38:42
@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}}, }