Analysis of the roles of RGD-binding integrins, α4/α9 integrins, α6 integrins, and CD9 in the interaction of the fertilin β (ADAM2) disintegrin domain with the mouse egg membrane

Xiaoling Zhu, Janice Perry Evans

Research output: Contribution to journalArticle

Abstract

Fertilin β (also known as ADAM2), a mammalian sperm protein that mediates gamete cell adhesion during fertilization, is a member of the ADAM protein family whose members have disintegrin domains with homology to integrin ligands found in snake venoms. Fertilin β utilizes an ECD sequence within its disintegrin domain to interact with the egg plasma membrane; the Asp is especially critical. Based on what is known about different integrin subfamilies and their ligands, we sought to characterize fertilin β binding sites on mouse eggs, focusing on integrin subfamilies that recognize short peptide sequences that include an Asp residue: the α58vIIb or RGD-binding subfamily α5β1, α8β1, αvβ1, αvβ3, αvβ5, αvβ6, αvβ8, and αIIbβ3) and the α49 subfamily (α4β1, α9β1, and α4β7). We tested peptide sequences known to perturb interactions mediated by these integrins in two different assays for fertilin β binding. Peptides with the sequence MLDG, which perturb α49 integrin-mediated interactions, significantly inhibit fertilin β binding to eggs, which suggests a role for a member of this integrin subfamily as a fertilin β receptor. RGD peptides, which perturb α58v/ αIIb integrin-mediated interactions, have partial inhibitory activity. The anti-α6 antibody GoH3 has little or no inhibitory activity. An antibody to the integrin-associated tetraspanin protein CD9 inhibits the binding of a multivalent presentation of fertilin β (immobilized on beads) but not soluble fertilin β, which we speculate has implications for the role of CD9 in the strengthening of fertilin β-mediated cell adhesion but not in initial ligand binding.

Original languageEnglish (US)
Pages (from-to)1193-1202
Number of pages10
JournalBiology of Reproduction
Volume66
Issue number4
StatePublished - 2002

Keywords

  • Fertilization
  • Gamete biology
  • Ovum
  • Sperm

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

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