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Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
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The FcεRI Signaling Cascade and Integrin Trafficking Converge at Patterned Ligand Surfaces
Devin L Wakefield1,2, David Holowka1, Barbara Baird3
1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853.
Molecular Biology of the Cell
|August 11, 2017
Summary
Cellular signaling pathways activated by the IgE receptor (FcεRI) are spatially targeted. Receptor engagement on patterned surfaces influences immune cell responses and protein recruitment, impacting cell adhesion and trafficking.
Area of Science:
- Immunology
- Cell Biology
- Biophysics
Background:
- The IgE receptor (FcεRI) plays a crucial role in allergic responses and immune cell signaling.
- Understanding how FcεRI signaling is spatially regulated is key to deciphering mast cell activation.
- Surface-patterned ligands offer a tool to investigate receptor engagement and downstream effects.
Purpose of the Study:
- To investigate the spatial targeting of early and downstream signaling events mediated by FcεRI.
- To determine how different ligand immobilization strategies (DNP-BSA vs. DNP-SLB) affect FcεRI distribution and signaling.
- To elucidate the role of actin polymerization and endosomal trafficking in FcεRI-mediated signaling.
Main Methods:
- Utilizing surface-patterned 2,4-dinitrophenyl (DNP) ligands (DNP-BSA and DNP-SLB) to engage FcεRI on RBL mast cells.
- Analyzing the spatial distribution of IgE-FcεRI and key signaling proteins (Syk, LAT, PLCγ1) using microscopy.
- Investigating the role of F-actin polymerization and recycling endosomes (REs) in the signaling cascade.
Main Results:
- IgE-FcεRI distribution differed between mobile (uniform on DNP-SLB) and immobilized (edge-concentrated on DNP-BSA) ligands.
- Spatial receptor distribution translated to the recruitment of early signaling proteins (Syk, LAT, PLCγ1).
- Actin polymerization was essential for LAT and PLCγ1 recruitment but not initial Syk recruitment.
- β1- and β3-integrins localized with FcεRI upon cell spreading, involving exocytosis of REs carrying integrins and fibronectin.
Conclusions:
- FcεRI engagement on patterned surfaces spatially targets signaling components, including integrins.
- Actin polymerization and recycling endosome trafficking are critical for downstream FcεRI signaling and integrin recruitment.
- This study reveals mechanisms of receptor-ligand interactions influencing immune cell activation and adhesion.
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