Mouse egg integrin α6β1functions as a sperm receptor

Abstract

Binding between sperm and egg plasma membranes is an essential step in fertilization. Whereas fertilin, a mammalian sperm surface protein, is involved in this crucial interaction, sperm receptors on the egg plasma membrane have not been identified. Because fertilin contains a predicted integrin ligand domain, we investigated the expression and function 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-blocking 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 staining 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 binding.

Regulation of cellular adhesion molecule expression in murine oocytes, peri-implantation and post-implantation embryos

“…Several integrin subunits are expressed on human and/or murine preimplantation embryos [7], [8]. Their function in embryonic development is not fully understood, but some, such as the α5 chain, are clearly individually important after implantation [26], [27].…”

“…Although cadherins are thought to be primarily responsible for the cell-cell adhesion seen in early vertebrate embryos [4], [6], a variety of integrin subunits have been detected on mouse and human preand peri-implantation embryos, including 1, 3, 5, 6, 7, V, 1, 3, 4, 5 [7][8][9]], suggesting that these molecules may play a role in embryonic development.…”

Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

“…Global deletion of Itgb1 in mice results in lethality during early post-implantation [35,36]. We thus exam- ined the effect of partial and complete elimination of Itgb1 in dorsal telencephalic progenitors by crossing the Itgb1 f/f or Itgb1 f/+ mice [37] with the Emx1-Cre transgenic mice [38], respectively.…”

Chronological gene expression of ADAMs during testicular development: Prespermatogonia (gonocytes) express fertilin β (ADAM2)

“…A proteolytic processing mechanism removes the pro-and metalloprotease domains, displaying the disintegrin domain at the N-terminus of the fertilin ␣ and ␤ Lum and Blobel, 1997). Peptides containing the disintegrin domain are known to bind to ␣II␤3 integrin present in platelets (Adler et al, 1991) and fertilin ␤ has been shown to bind to ␣6␤1 integrin present on the egg plasma membrane (Almeida et al, 1995). ␣3␤1 and ␣6␤1 integrins are expressed by both testicular somatic and spermatogenic cells (Schaller et al, 1993;Salanova et al, 1995) during fetal and postnatal testicular development (Frojdman and Pelliniemi, 1994) and in Sertoli-PSG cocultures (Rosselot et al, 2001).…”

“…In addition to fertilin ␣ and fertilin ␤, the gene expression of several members of the ADAM family has been detected in somatic and spermatogenic cell components of prepubertal and adult rat testis and other organs (Frayne et al, 1997). An ␣6␤1 integrin receptor on mouse egg plasma membrane acts as the sperm receptor to which the disintegrin domain of fertilin ␤ binds (Almeida et al, 1995). It has been reported that fertilin ␤ but not fertilin ␣ displays adhesive activity by interacting with ␤1 integrin (Evans et al, 1997).…”