Signalling, sorting and scaffolding adaptors for Toll-like receptors.

Abstract

Toll-like receptors (TLRs) are danger-sensing receptors that typically propagate self-limiting inflammatory responses, but can unleash uncontrolled inflammation in non-homeostatic or disease settings. Activation of TLRs by pathogen- and/or host-derived stimuli triggers a range of signalling and transcriptional pathways to programme inflammatory and anti-microbial responses, including the production of a suite of inflammatory cytokines and other mediators. Multiple sorting and signalling adaptors are recruited to receptor complexes on the plasma membrane or endosomes where they act as scaffolds for downstream signalling kinases and effectors at these sites. So far, seven proximal TLR adaptors have been identified: MyD88, MAL, TRIF (also known as TICAM1), TRAM (TICAM2), SARM (SARM1), BCAP (PIK3AP1) and SCIMP. Most adaptors tether directly to TLRs through homotypic Toll/interleukin-1 receptor domain (TIR)-TIR interactions, whereas SCIMP binds to TLRs through an atypical TIR-non-TIR interaction. In this Review, we highlight the key roles for these adaptors in TLR signalling, scaffolding and receptor sorting and discuss how the adaptors thereby direct the differential outcomes of TLR-mediated responses. We further summarise TLR adaptor regulation and function, and make note of human diseases that might be associated with mutations in these adaptors.

• Authors: Lin Luo, Richard M Lucas, Liping Liu, Jennifer L Stow
• Journal: Journal of cell science (J Cell Sci) Vol. 133 Issue 5 (12 30 2019) ISSN: 1477-9137 [Electronic] England
• PMID: 31889021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2020. Published by The Company of Biologists Ltd.

Chemical References

• Adaptor Proteins, Vesicular Transport
• Cytokines
• Receptors, Interleukin-1
• Toll-Like Receptors

Topics

• Adaptor Proteins, Vesicular Transport (genetics, metabolism)
• Animals
• Cytokines (genetics, metabolism)
• Humans
• Protein Binding
• Protein Transport
• Receptors, Interleukin-1 (genetics, metabolism)
• Signal Transduction
• Toll-Like Receptors (genetics, metabolism)