title: Ligand-binding specificities of laminin-binding integrins: a comprehensive survey of laminin-integrin interactions using recombinant alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4 integrins.
abstract: The interactions of cells with basement membranes are primarily mediated via the engagement of laminins by a group of integrin family proteins, including integrins alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4. To explore the ligand-binding specificities of these laminin-binding integrins, we produced these integrins, including two alpha7beta1 splice variants (alpha7X1beta1 and alpha7X2beta1), as soluble recombinant proteins and determined their binding specificities and affinities toward a panel of purified laminin isoforms containing distinct alpha chains. Among the five laminin-binding integrins investigated, alpha3beta1 and alpha6beta4 exhibited a clear specificity for laminin-332 (alpha3beta3gamma2) and laminin-511 (alpha5beta1gamma1)/521 (alpha5beta2gamma1), while integrin alpha6beta1 showed a broad specificity, binding to all laminin isoforms with a preference for laminin-111 (alpha1beta1gamma1), laminin-332 and laminin-511/521. The two alpha7beta1 variants were distinct from alpha3beta1, alpha6beta1 and alpha6beta4 in that they did not bind to laminin-332. alpha7X1beta1 bound to all laminins, except laminin-332, with a preference for laminin-211 (alpha2beta1gamma1)/221 (alpha2beta2gamma1) and laminin-511/521, while alpha7X2beta1 bound preferentially to laminin-111 and laminin-211/221. Laminin-511/521 was the most preferred ligand for all the laminin-binding integrins, except for alpha7X2beta1, whereas laminin-411 was the poorest ligand, capable of binding to alpha6beta1 and alpha7X1beta1 with only modest binding affinities. These comprehensive analyses of the interactions between laminin-binding integrins and a panel of laminins clearly demonstrate that the isoforms of both integrins and laminins differ in their binding specificities and affinities, and provide a molecular basis for better understanding of the adhesive interactions of cells with basement membranes of defined laminin compositions.
authors.affiliation: Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Nishiuchi
authors.forename: Junichi
authors.initials: J
authors.lastname: Takagi
authors.forename: Maria
authors.initials: M
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ido
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yagi
authors.forename: Noriko
authors.initials: N
authors.lastname: Sanzen
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tsuji
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamada
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Sekiguchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism*; D039121:Integrin alpha6beta1 / Q000235:genetics / Q000378:metabolism*; D039161:Integrin alpha6beta4 / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D039201:Integrin alpha3beta1; D039121:Integrin alpha6beta1; D039161:Integrin alpha6beta4; D016023:Integrins; D007797:Laminin; D008024:Ligands; D020033:Protein Isoforms; D021122:Protein Subunits; D011994:Recombinant Proteins; C082908:integrin alpha7beta1