Dataset Information

Ataxin-3 Links NOD2 and TLR2 Mediated Innate Immune Sensing and Metabolism in Myeloid Cells.

ABSTRACT: The interplay between NOD2 and TLR2 following recognition of components of the bacterial cell wall peptidoglycan is well-established, however their role in redirecting metabolic pathways in myeloid cells to degrade pathogens and mount antigen presentation remains unclear. We show NOD2 and TLR2 mediate phosphorylation of the deubiquitinase ataxin-3 via RIPK2 and TBK1. In myeloid cells ataxin-3 associates with the mitochondrial cristae protein MIC60, and is required for oxidative phosphorylation. Depletion of ataxin-3 leads to impaired induction of mitochondrial reactive oxygen species (mROS) and defective bacterial killing. A mass spectrometry analysis of NOD2/TLR2 triggered ataxin-3 deubiquitination targets revealed immunometabolic regulators, including HIF-1? and LAMTOR1 that may contribute to these effects. Thus, we define how ataxin-3 plays an essential role in NOD2 and TLR2 sensing and effector functions in myeloid cells.

SUBMITTER: Chapman TP

PROVIDER: S-EPMC6659470 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Ataxin-3 Links NOD2 and TLR2 Mediated Innate Immune Sensing and Metabolism in Myeloid Cells.

Chapman Thomas P TP Corridoni Daniele D Shiraishi Seiji S Pandey Sumeet S Aulicino Anna A Wigfield Simon S do Carmo Costa Maria M Thézénas Marie-Laëtitia ML Paulson Henry H Fischer Roman R Kessler Benedikt M BM Simmons Alison A

Frontiers in immunology 20190719

The interplay between NOD2 and TLR2 following recognition of components of the bacterial cell wall peptidoglycan is well-established, however their role in redirecting metabolic pathways in myeloid cells to degrade pathogens and mount antigen presentation remains unclear. We show NOD2 and TLR2 mediate phosphorylation of the deubiquitinase ataxin-3 via RIPK2 and TBK1. In myeloid cells ataxin-3 associates with the mitochondrial cristae protein MIC60, and is required for oxidative phosphorylation. ...[more]

PMID: 31379806

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Dataset Information

Ataxin-3 Links NOD2 and TLR2 Mediated Innate Immune Sensing and Metabolism in Myeloid Cells.

Publications

Ataxin-3 Links NOD2 and TLR2 Mediated Innate Immune Sensing and Metabolism in Myeloid Cells.

Similar Datasets

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