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Published on: May 26, 2011
The alpha(4) integrin subunit Tyr(187) has a key role in alpha(4)beta(7)-dependent cell adhesion
N Ruiz-Velasco1, M Guerrero-Esteo, M J Briskin
1Department of Immunology, Centro de Investigaciones Biológicas, Velázquez 144, 28006 Madrid, Spain.
The Journal of Biological Chemistry
|March 4, 2000
Summary
The integrin alpha(4)beta(7) receptor
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Integrin alpha(4)beta(7) is crucial for lymphocyte homing to Peyer's patches and inflammation sites.
- This integrin functions as the cell adhesion receptor for mucosal vascular addressin MAdCAM-1.
Purpose of the Study:
- To pinpoint specific amino acids in the alpha(4) subunit critical for the alpha(4)beta(7)/MAdCAM-1 interaction.
- To understand the role of these residues in leukocyte adhesion and potential therapeutic targeting.
Main Methods:
- Mutant alpha(4) and wild-type beta(7) chains were expressed in K562 cells.
- Cell adhesion assays were performed using soluble MAdCAM-1 (sMAdCAM-1-Ig) and CS-1/fibronectin.
- The impact of mutations on ligand binding and adhesion was analyzed, with and without Mn(2+) supplementation.
Main Results:
- Mutation of alpha(4) Tyr(187) significantly reduced adhesion to sMAdCAM-1-Ig and abolished adhesion to CS-1/fibronectin.
- Mutations at alpha(4) Gln(152)Asp(153) affected adhesion but not MAdCAM-1 binding, with adhesion restored by Mn(2+).
- Mutations at alpha(4) Asn(123)Glu(124) had no effect on adhesion to sMAdCAM-1-Ig.
Conclusions:
- Alpha(4) Tyr(187) is identified as a key residue in alpha(4)beta(7) receptor-ligand interactions.
- This residue plays a vital role in alpha(4)beta(7)-mediated leukocyte adhesion.
- The findings suggest alpha(4) Tyr(187) as a potential therapeutic target for inflammatory diseases.
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