Journal article
SCIMP is a spatiotemporal transmembrane scaffold for Erk1/2 to direct pro-inflammatory signaling in TLR-activated macrophages
Cell Reports, Vol.36(10), Art. 109662
2021
Abstract
Immune cells are armed with Toll-like receptors (TLRs) for sensing and responding to pathogens and other danger cues. The role of extracellular-signal-regulated kinases 1/2 (Erk1/2) in TLR signaling remains enigmatic, with both pro- and anti-inflammatory functions described. We reveal here that the immune-specific transmembrane adaptor SCIMP is a direct scaffold for Erk1/2 in TLR pathways, with high-resolution, live-cell imaging revealing that SCIMP guides the spatial and temporal recruitment of Erk2 to membrane ruffles and macropinosomes for pro-inflammatory TLR4 signaling. SCIMP-deficient mice display defects in Erk1/2 recruitment to TLR4, c-Fos activation, and pro-inflammatory cytokine production, with these effects being phenocopied by Erk1/2 signaling inhibition. Our findings thus delineate a selective role for SCIMP as a key scaffold for the membrane recruitment of Erk1/2 kinase to initiate TLR-mediated pro-inflammatory responses in macrophages.
Details
- Title
- SCIMP is a spatiotemporal transmembrane scaffold for Erk1/2 to direct pro-inflammatory signaling in TLR-activated macrophages
- Authors/Creators
- R.M. Lucas (Author/Creator)L. Liu (Author/Creator)J.E.B. Curson (Author/Creator)Y.W.H. Koh (Author/Creator)N. Tuladhar (Author/Creator)N.D. Condon (Author/Creator)K. Das Gupta (Author/Creator)S.S. Burgener (Author/Creator)K. Schroder (Author/Creator)E. Ingley (Author/Creator)M.J. Sweet (Author/Creator)J.L. Stow (Author/Creator)L. Luo (Author/Creator)
- Publication Details
- Cell Reports, Vol.36(10), Art. 109662
- Publisher
- Elsevier Inc.
- Identifiers
- 991005544454807891
- Copyright
- © 2021 The Authors.
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
17 File views/ downloads
131 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.609 Toll-like Receptors
- Web Of Science research areas
- Cell Biology
- ESI research areas
- Molecular Biology & Genetics