Multifaceted roles and regulation of nucleotide-binding oligomerization domain containing proteins

Charneal L Dixon; Amy Wu; Gregory D Fairn

doi:10.3389/fimmu.2023.1242659

Multifaceted roles and regulation of nucleotide-binding oligomerization domain containing proteins

Front Immunol. 2023 Oct 5:14:1242659. doi: 10.3389/fimmu.2023.1242659. eCollection 2023.

Authors

Charneal L Dixon¹, Amy Wu², Gregory D Fairn^{1

2

3}

Affiliations

¹ Department of Pathology, Dalhousie University, Halifax, NS, Canada.
² Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
³ Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada.

Abstract

Nucleotide-binding oligomerization domain-containing proteins, NOD1 and NOD2, are cytosolic receptors that recognize dipeptides and tripeptides derived from the bacterial cell wall component peptidoglycan (PGN). During the past two decades, studies have revealed several roles for NODs beyond detecting PGN fragments, including activation of an innate immune anti-viral response, NOD-mediated autophagy, and ER stress induced inflammation. Recent studies have also clarified the dynamic regulation of NODs at cellular membranes to generate specific and balanced immune responses. This review will describe how NOD1 and NOD2 detect microbes and cellular stress and detail the molecular mechanisms that regulate activation and signaling while highlighting new evidence and the impact on inflammatory disease pathogenesis.

Keywords: Crohn’s; NF-κB; NOD1; NOD2; inflammation; peptidoglycan.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Inflammation
Nod Signaling Adaptor Proteins* / metabolism
Nod1 Signaling Adaptor Protein*
Nod2 Signaling Adaptor Protein / metabolism
Nucleotides / metabolism

Substances

Nod Signaling Adaptor Proteins
Nod1 Signaling Adaptor Protein
Nod2 Signaling Adaptor Protein
Nucleotides

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. CD is supported in part by the Dalhousie Medical Research Foundation Accelerator Award. This work was supported by a Canadian Institutes of Health Research Foundation Project Grant (PJT166010) and an Innovator Award from the Kenneth Rainin Foundation to GF. GF also holds a Tier 1 Canada Research Chair in Multiomics of Lipids and Innate Immunity.