Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor.
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.
Almeida
E A
EA
Department of Cell Biology, University of Virginia, Charlotteville 22908, USA.
Huovila
A P
AP
Sutherland
A E
AE
Stephens
L E
LE
Calarco
P G
PG
Shaw
L M
LM
Mercurio
A M
AM
Sonnenberg
A
A
Primakoff
P
P
Myles
D G
DG
White
J M
JM
D051722:ADAM Proteins; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D002459:Cell Fusion; D017931:DNA Primers; D005260:Female; D000072196:Fertilins; D015870:Gene Expression; D039121:Integrin alpha6beta1; D016023:Integrins / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D008666:Metalloendopeptidases; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010063:Ovum / Q000166:cytology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D017474:Receptors, Laminin / Q000502:physiology; D013084:Sperm-Ovum Interactions / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D017931:DNA Primers; D039121:Integrin alpha6beta1; D016023:Integrins; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017474:Receptors, Laminin; C035027:egg surface sperm receptor; C059453:RGES peptide; C049554:glycyl-arginyl-glycyl-aspartyl-serine; D051722:ADAM Proteins; D000072196:Fertilins; D008666:Metalloendopeptidases