Integrins can exist in different functional states with low or high binding
capacity for particular ligands. We previously provided evidence that the
integrin alpha 6 beta 1, on mouse eggs and on alpha 6-transfected cells, in
teracted with the disintegrin domain of the sperm surface protein ADAM 2 (f
ertilin beta). In the present study we tested the hypothesis that different
states of alpha 6 beta 1 interact with fertilin and laminin, an extracellu
lar matrix ligand for alpha 6 beta 1. Using alpha 6-transfected cells we fo
und that treatments (e.g., with phorbol myristate acetate or MnCl2) that in
creased adhesion to laminin inhibited sperm binding. Conversely, treatments
that inhibited laminin adhesion increased sperm binding. Next, we compared
the ability of fluorescent beads coated with either fertilin beta or with
the laminin E8 fragment to bind to eggs. In Ca2+-containing media, fertilin
beta beads bound to eggs via an interaction mediated by the disintegrin lo
op of fertilin beta and by the alpha 6 integrin subunit, In Ca2+-containing
media, laminin E8 beads did not bind to eggs. Treatment of eggs with phorb
ol myristate acetate or with the actin disrupting agent, latrunculin A, inh
ibited fertilin bead binding, but did not induce laminin E8 bead binding. T
reatment of eggs with Mn2+ dramatically increased laminin E8 bead binding,
and inhibited fertilin bead binding. Our results provide the first evidence
that different states of an integrin (alpha 6 beta 1) can interact with an
extracellular matrix ligand (laminin) or a membrane-anchored cell surface
ligand (ADAM 2).