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.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

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 PØ,Eijkelkamp N

doi

10.1371/journal.pbio.2003452

subject

Has Abstract

pub_date

2018-02-14 00:00:00

pages

e2003452

issue

2

eissn

1544-9173

issn

1545-7885

pii

pbio.2003452

journal_volume

16

pub_type

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