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The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces

We examined the spatial targeting of early and downstream signaling mediated by the immunoglobulin E (IgE) receptor (FcεRI) in RBL mast cells using surface-patterned 2,4-dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin...

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Autores principales: Wakefield, Devin L., Holowka, David, Baird, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687038/
https://www.ncbi.nlm.nih.gov/pubmed/28794269
http://dx.doi.org/10.1091/mbc.E17-03-0208
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author Wakefield, Devin L.
Holowka, David
Baird, Barbara
author_facet Wakefield, Devin L.
Holowka, David
Baird, Barbara
author_sort Wakefield, Devin L.
collection PubMed
description We examined the spatial targeting of early and downstream signaling mediated by the immunoglobulin E (IgE) receptor (FcεRI) in RBL mast cells using surface-patterned 2,4-dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin (DNP-BSA) or mobile in a supported lipid bilayer (DNP-SLB). Although soluble anti-DNP IgE binds uniformly across features for both pattern types, IgE bound to FcεRI on cells shows distinctive distributions: uniform for DNP-SLB and edge concentrated for DNP-BSA. These distributions of IgE-FcεRI propagate to the spatial recruitment of early signaling proteins, including spleen tyrosine kinase (Syk), linker for activation of T-cells (LAT), and activated phospholipase C gamma 1 (PLCγ1), which all localize with engaged receptors. We found stimulated polymerization of F-actin is not required for Syk recruitment but is progressively involved in the recruitment of LAT and PLCγ1. We further found β1- and β3-integrins colocalize with IgE-FcεRI at patterned ligand surfaces as cells spread. This recruitment corresponds to directed exocytosis of recycling endosomes (REs) containing these integrins and their fibronectin ligand. Together our results show targeting of signaling components, including integrins, to regions of clustered IgE-FcεRI in processes that depend on stimulated actin polymerization and outward trafficking of REs.
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spelling pubmed-56870382018-01-22 The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces Wakefield, Devin L. Holowka, David Baird, Barbara Mol Biol Cell Articles We examined the spatial targeting of early and downstream signaling mediated by the immunoglobulin E (IgE) receptor (FcεRI) in RBL mast cells using surface-patterned 2,4-dinitrophenyl (DNP) ligands. Micron-sized features of DNP are presented as densely immobilized conjugates of bovine serum albumin (DNP-BSA) or mobile in a supported lipid bilayer (DNP-SLB). Although soluble anti-DNP IgE binds uniformly across features for both pattern types, IgE bound to FcεRI on cells shows distinctive distributions: uniform for DNP-SLB and edge concentrated for DNP-BSA. These distributions of IgE-FcεRI propagate to the spatial recruitment of early signaling proteins, including spleen tyrosine kinase (Syk), linker for activation of T-cells (LAT), and activated phospholipase C gamma 1 (PLCγ1), which all localize with engaged receptors. We found stimulated polymerization of F-actin is not required for Syk recruitment but is progressively involved in the recruitment of LAT and PLCγ1. We further found β1- and β3-integrins colocalize with IgE-FcεRI at patterned ligand surfaces as cells spread. This recruitment corresponds to directed exocytosis of recycling endosomes (REs) containing these integrins and their fibronectin ligand. Together our results show targeting of signaling components, including integrins, to regions of clustered IgE-FcεRI in processes that depend on stimulated actin polymerization and outward trafficking of REs. The American Society for Cell Biology 2017-11-07 /pmc/articles/PMC5687038/ /pubmed/28794269 http://dx.doi.org/10.1091/mbc.E17-03-0208 Text en © 2017 Wakefield et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Wakefield, Devin L.
Holowka, David
Baird, Barbara
The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces
title The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces
title_full The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces
title_fullStr The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces
title_full_unstemmed The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces
title_short The FcεRI signaling cascade and integrin trafficking converge at patterned ligand surfaces
title_sort fcεri signaling cascade and integrin trafficking converge at patterned ligand surfaces
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687038/
https://www.ncbi.nlm.nih.gov/pubmed/28794269
http://dx.doi.org/10.1091/mbc.E17-03-0208
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