Alternative splice variants of alpha 7 beta 1 integrin selectively recognize different laminin isoforms.
The integrin alpha(7)beta(1) occurs in several cytoplasmic (alpha(7A), alpha(7B)) and extracellular splice variants (alpha(7X1), alpha(7X2)), which are differentially expressed during development of skeletal and heart muscle. The extracellular variants result from the alternative splicing of exons X1 and X2, corresponding to a segment within the putative ligand binding domain. To study the specificity and affinity of the X1/X2 variants to different laminin isoforms, soluble alpha(7)beta(1) complexes were prepared by recombinant coexpression of the extracellular domains of the alpha- and beta-subunits. The binding of these complexes to purified ligands was measured by solid phase binding assays. Surprisingly, the alternative splice variants revealed different and specific affinities to different laminin isoforms. While the alpha(7X2) variant bound much more strongly to laminin-1 than the alpha(7X1) variant, the latter showed a high affinity binding to laminins-8 and -10/11. Laminin-2, the major laminin isoform in skeletal muscle, was recognized by both variants, whereas none of the two variants were able to interact with laminin-5. A specific blocking antibody inhibited the binding of both variants to all laminins tested, indicating the involvement of common epitopes in alpha(7X1)beta(1) and alpha(7X2)beta(1). Because laminin-8 and -10/11 as well as alpha(7X1) are expressed in developing skeletal and cardiac muscle, these findings suggest that alpha(7X1)beta(1) may represent a physiological receptor with novel specificities for laminin-8 and -10.
von der Mark
Helga
H
Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, Department of Experimental Medicine I, 91054 Erlangen, Germany.
Williams
Inka
I
Wendler
Olaf
O
Sorokin
Lydia
L
von der Mark
Klaus
K
Pöschl
Ernst
E
D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D014644:Genetic Variation; D006801:Humans; D016023:Integrins / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016023:Integrins; D007797:Laminin; D020033:Protein Isoforms; D021122:Protein Subunits; D011994:Recombinant Proteins; C121346:laminin 1; C082908:integrin alpha7beta1