Characterization of the Ligand-Binding Specificities of Integrin  3 1 and  6 1 Using a Panel of Purified Laminin Isoforms Containing Distinct   Chains

Abstract

Integrins alpha3beta1 and alpha6beta1 are two major laminin receptors expressed on the surface of mammalian cells. Interactions of cells with laminins through these integrins play important roles in cell adhesion, differentiation, motility, and matrix assembly. To determine the binding specificity and affinity of these integrins toward various types of laminins at the level of direct protein-protein interactions, we purified integrins alpha3beta1 and alpha6beta1 from human placenta, and examined their binding to a panel of laminin isoforms, each containing distinct alpha chains (i.e., laminin-1, laminin-2/4, laminin-5, laminin-8, and laminin-10/11). Integrin alpha3beta1 showed clear specificity for laminin-5 and laminin-10/11, with no significant binding to laminin-1, laminin-2/4, and laminin-8. In contrast, integrin alpha6beta1 showed a broad spectrum of specificity, with apparent binding affinity in the following order: laminin-10/11 > laminin-5 > laminin-1 > laminin-2/4 congruent with laminin-8. Integrin titration assays demonstrated that laminin-10/11 was the most preferred ligand among the five distinct laminin isoforms for both alpha3beta1 and alpha6beta1 integrins. Given that laminin-10/11 is the major basement membrane component of many adult tissues, the interaction of laminin-10/11 with these integrins should play a central role in the adhesive interactions of epithelial cells with underlying basement membranes.

Regulation of Integrin Endocytic Recycling and Chemotactic Cell Migration by Syntaxin 6 and VAMP3 Interaction

“…6B). Since a3b1 integrin binds to laminin-5 and laminin-10/11, but not to laminin-1 (Delwel et al, 1994;Kreidberg, 2000;Nishiuchi et al, 2003), these data suggest that STX6 may be involved in the trafficking of other laminin receptors such as a6b1 integrin, which binds to laminin-1 (Delwel et al, 1994).…”

Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

“…It was most highly expressed by PBs in URI and Strep, and was absent in most clusters enriched in CeD. α6β1 is a receptor for laminins (44), extracellular matrix components comprised of multiple isoforms whose expression varies in different tissues (45). α6 binding to laminins is thought to play an important role in platelet-mediated thrombosis (46).…”

Laminins affect T cell trafficking and allograft fate

“…Laminins have a variety of structural, adhesive, and stimulatory functions, and their importance is underlined by the findings that laminin α4-null mice experience extensive hemorrhage and impaired microvascular growth (32), and that laminin α5 deficiency results in embryonic lethality (52). The G domains of both laminin α4 and α5 serve as ligands for T cell integrins, promoting and affecting T cell trafficking both as T cells leave the HEV and within the LN parenchyma (74)(75)(76). We observed laminin α5 but not laminin α4 to have a modest impact on T cell proliferation and activation, and negligible impact on Treg differentiation, following coculture with anti-CD3, IL-2, and APC stimulation (data not shown).…”