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Regulation of IL-1 signaling through control of focal adhesion assembly.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2018 Jun; Vol. 32 (6), pp. 3119-3132. Date of Electronic Publication: 2018 Jan 22. - Publication Year :
- 2018
-
Abstract
- IL-1 signaling is adhesion-restricted in many cell types, but the mechanism that drives it is not defined. We screened for proteins recruited to nascent adhesions in IL-1-treated human fibroblasts with tandem mass tag-mass spectrometry. We used fibronectin bead preparations to enrich 10 actin-associated proteins. There was a 1.2 times log 2-fold enrichment of actin capping protein (ACP) at 30 min after IL-1 stimulation. Knockdown (KD) of ACP by siRNA reduced IL-1-induced ERK activation(by 56%, matrix metalloproteinase-3 (MMP-3) expression by 48%, and MMP-9 expression by 62% (in all reductions, P < 0.01). Confocal or structured illumination microscopy showed that ACP was diffused throughout the cytosol but strongly accumulated at the ruffled border of spreading cells. ACP colocalized with nascent paxillin- and vinculin-containing adhesions at the ruffled border, but not with mature adhesions in the center. ACP KD promoted the formation of large, stable adhesions. Immunoprecipitation and proximity ligation analysis showed that ACP was associated with the IL-1 signal transduction proteins myeloid differentiation factor 88 (MyD88) and IL-1 receptor-associated kinase (IRAK) at the ruffled border of the leading edge. IL-1-induced phospho-ERK and MyD88 or IRAK colocalized at the leading edge. We concluded that ACP is required for recruitment and function of IL-1 signaling complexes in nascent adhesions at the leading edge of the cell.-Wang, Q., Delcorde, J., Tang, T., Downey, G. P., McCulloch, C. A. Regulation of IL-1 signaling through control of focal adhesion assembly.
- Subjects :
- Actin Capping Proteins genetics
Fibroblasts cytology
Focal Adhesions genetics
Gene Knockdown Techniques
Humans
Interleukin-1 genetics
Interleukin-1 Receptor-Associated Kinases genetics
Interleukin-1 Receptor-Associated Kinases metabolism
Myeloid Differentiation Factor 88 genetics
Myeloid Differentiation Factor 88 metabolism
Actin Capping Proteins metabolism
Fibroblasts metabolism
Focal Adhesions metabolism
Interleukin-1 metabolism
MAP Kinase Signaling System physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 32
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 29401618
- Full Text :
- https://doi.org/10.1096/fj.201700966R