Binding between sperm and egg plasma membranes is an essential step in
fertilization. Whereas fertilin, a mammalian sperm surface protein, i
s involved in this crucial interaction, sperm receptors on the egg pla
sma membrane have not been identified. Because fertilin contains a pre
dicted integrin ligand domain, we investigated the expression and func
tion of integrin subunits in unfertilized mouse eggs. Polymerase chain
reactions detected mRNAs for alpha 5, alpha 6, alpha v, beta 1, beta
3, and beta 5. Immunofluorescence revealed alpha 6 beta 1 and alpha v
beta 3 on the plasma membrane. GoH3, a function-blocking anti-alpha 6
monoclonal antibody, abolished sperm binding, but a nonfunction-blocki
ng anti-alpha 6 monoclonal antibody, a function-blocking anti-alpha v
beta 3 polyclonal antibody, and an RGD peptide had no effect. Somatic
cells bound sperm avidly, but only if they expressed alpha 6 beta 1. A
peptide analog of the fertilin integrin ligand domain inhibited sperm
binding to eggs and alpha 6 beta 1(+) cells and diminished GoH3 stain
ing of eggs. Our results indicate a novel role for the integrin alpha
6 beta 1 as a cell-cell adhesion receptor that mediates sperm-egg bind
ing.