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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

16 Citations (Scopus)

3 Downloads (Pure)

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
Article number	e2003452
Journal	PLoS Biology
Volume	16
Issue number	2
DOIs	https://doi.org/10.1371/journal.pbio.2003452
Publication status	Published - 14 Feb 2018

Access to Document

10.1371/journal.pbio.2003452

journal.pbio.2003452Final published version, 36.1 MB

Cite this

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

@article{874bf3e0c2e74188a9f189cf45aee9a8,

title = "Identification of FAM173B as a protein methyltransferase promoting chronic pain",

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.",

author = "Willemen, {Hanneke L.D.M.} and Annemieke Kavelaars and Judith Prado and Mirjam Maas and Sabine Versteeg and Nellissen, {Lara J.J.} and Jeshua Tromp and {Gonzalez Cano}, Rafael and Wenjun Zhou and Jakobsson, {Magnus E.} and J{\c e}drzej Ma{\l}ecki and George Posthuma and Habib, {Abdella M.} and Heijnen, {Cobi J.} and P{\aa}l Falnes and Niels Eijkelkamp",

year = "2018",

month = feb,

day = "14",

doi = "10.1371/journal.pbio.2003452",

language = "English",

volume = "16",

journal = "PLoS Biology",

issn = "1544-9173",

publisher = "Public Library of Science",

number = "2",

}

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

TY - JOUR

T1 - Identification of FAM173B as a protein methyltransferase promoting chronic pain

AU - Willemen, Hanneke L.D.M.

AU - Kavelaars, Annemieke

AU - Prado, Judith

AU - Maas, Mirjam

AU - Versteeg, Sabine

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

PY - 2018/2/14

Y1 - 2018/2/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85043709310&partnerID=8YFLogxK

U2 - 10.1371/journal.pbio.2003452

DO - 10.1371/journal.pbio.2003452

M3 - Article

C2 - 29444090

SN - 1544-9173

VL - 16

JO - PLoS Biology

JF - PLoS Biology

IS - 2

M1 - e2003452

ER -

Identification of FAM173B as a protein methyltransferase promoting chronic pain

Abstract

Access to Document

Other files and links

Fingerprint

Cite this