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 Falnes; Niels Eijkelkamp

doi:10.1371/journal.pbio.2003452

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 Falnes, Niels Eijkelkamp

Symptom Research CAO

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19 Scopus citations

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 language	English (US)
Article number	e2003452
Journal	PLoS biology
Volume	16
Issue number	2
DOIs	https://doi.org/10.1371/journal.pbio.2003452
State	Published - Feb 14 2018

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology
General Agricultural and Biological Sciences

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10.1371/journal.pbio.2003452

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Willemen, H. L. D. M., Kavelaars, A., Prado, J., Maas, M., Versteeg, S., Nellissen, L. J. J., Tromp, J., Gonzalez Cano, R., Zhou, W., Jakobsson, M. E., Małecki, J., Posthuma, G., Habib, A. M., Heijnen, C. J., Falnes, P., & Eijkelkamp, N. (2018). Identification of FAM173B as a protein methyltransferase promoting chronic pain. PLoS biology, 16(2), Article e2003452. https://doi.org/10.1371/journal.pbio.2003452

Willemen, HLDM, Kavelaars, A, Prado, J, Maas, M, Versteeg, S, Nellissen, LJJ, Tromp, J, Gonzalez Cano, R, Zhou, W, Jakobsson, ME, Małecki, J, Posthuma, G, Habib, AM, Heijnen, CJ, Falnes, P & Eijkelkamp, N 2018, 'Identification of FAM173B as a protein methyltransferase promoting chronic pain', PLoS biology, vol. 16, no. 2, e2003452. https://doi.org/10.1371/journal.pbio.2003452

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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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AU - Nellissen, Lara J.J.

AU - Tromp, Jeshua

AU - Gonzalez Cano, Rafael

AU - Zhou, Wenjun

AU - Jakobsson, Magnus E.

AU - Małecki, Jędrzej

AU - Posthuma, George

AU - Habib, Abdella M.

AU - Heijnen, Cobi J.

AU - Falnes, Pål

AU - Eijkelkamp, Niels

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Identification of FAM173B as a protein methyltransferase promoting chronic pain

Abstract

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