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An alternately spliced mRNA encoding functional domains of murine MAdCAM-1
S G Schiffer1, E Day, S M Latanision
1Biogen, Inc., Cambridge, MA 02142, USA.
Abstract:
cDNA clones representing a small (0.8 kb) form of murine mucosal addressin cell adhesion molecule-1 (MAdCAM-1) mRNA were obtained and sequenced. The sequence was identical to the published 1.6 kb murine MAdCAM-1 cDNA sequence, except that 432 nucleotides encoding the mucin-like and IgA-homologous portions were deleted. This cDNA most likely represents an alternately spliced mRNA. Substantial amounts of both the short and long MAdCAM-1 mRNAs are present in murine mesenteric lymph node. Ig fusion proteins displaying either the short or long forms of MAdCAM-1 can bind Mn(++)-activated JY cells bearing human alpha 4 beta 7 integrin, indicating that the two N-terminal Ig-like domains of MAdCAM-1 are sufficient to bind its integrin counter-receptor.
Insights
Researchers identified a shorter form of murine mucosal addressin cell adhesion molecule-1 (MAdCAM-1) mRNA, likely due to alternative splicing. This shorter MAdCAM-1 variant retains the ability to bind the alpha 4 beta 7 integrin.
Area of Science:
- Immunology
- Molecular Biology
- Cell Adhesion
Background:
- Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) is crucial for lymphocyte homing to mucosal tissues.
- MAdCAM-1 mediates leukocyte-endothelial cell interactions through its integrin counter-receptor, alpha 4 beta 7.
Purpose of the Study:
- To characterize a newly identified short form of murine MAdCAM-1.
- To investigate the functional significance of the short MAdCAM-1 variant in ligand binding.
Main Methods:
- cDNA cloning and sequencing of short and long MAdCAM-1 mRNA variants.
- Expression of MAdCAM-1 Ig fusion proteins.
- Binding assays using JY cells expressing alpha 4 beta 7 integrin.
Main Results:
- A short (0.8 kb) MAdCAM-1 cDNA was identified, differing from the long form by deletion of 432 nucleotides.
- This short form likely arises from alternative mRNA splicing.
- Both short and long MAdCAM-1 forms are expressed in murine mesenteric lymph nodes.
- Immunoglobulin fusion proteins of both MAdCAM-1 variants bind to alpha 4 beta 7 integrin on JY cells.
Conclusions:
- The two N-terminal Ig-like domains of MAdCAM-1 are sufficient for binding alpha 4 beta 7 integrin.
- Alternative splicing generates functional MAdCAM-1 variants involved in immune cell trafficking.