Mediation of sperm-egg fusion: evidence that mouse egg alpha6beta1 integrin is the receptor for sperm fertilinbeta.
BACKGROUND



BACKGROUND
A key step leading to fertilization is the binding of sperm to the egg plasma membrane. When a mammalian sperm reaches the egg plasma membrane, fertilinbeta, an extracellular sperm membrane protein, is believed to bind to an egg plasma membrane receptor triggering fusion. We set out to identify the fertilinbeta binding partner on the egg plasma membrane.


RESULTS
We synthesized an 125-labeled peptide with the consensus Asp-Glu-Cys-Asp (DECD) sequence of fertilinbeta's disintegrin domain. This peptide contains a benzophenone photoaffinity probe and inhibits sperm-egg fusion. Upon photoactivation in the presence of whole mouse eggs, a single polypeptide was covalently labeled. This polypeptide has been identified by immunoprecipitation as an alpha6 integrin complexed with beta1 integrin.


CONCLUSIONS
Our experiments establish that small peptides containing the consensus DECD sequence of sperm fertilinbeta bind specifically to an alpha6beta1 integrin receptor on the egg membrane. We conclude that fertilinbeta binds directly to the alpha6beta1 integrin on the egg surface and this partnership mediates sperm-egg fusion.
Chen
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Department of Chemistry, State University of New York, Stony Brook 11794 3400, USA.
Sampson
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D051722:ADAM Proteins; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D000072196:Fertilins; D005306:Fertilization / Q000502:physiology; D006801:Humans; D039121:Integrin alpha6beta1; D016023:Integrins / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010063:Ovum / Q000378:metabolism / Q000502:physiology*; D010455:Peptides / Q000138:chemical synthesis / Q000502:physiology; D019920:Photoaffinity Labels / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013084:Sperm-Ovum Interactions / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology*
D039121:Integrin alpha6beta1; D016023:Integrins; D008562:Membrane Glycoproteins; D010455:Peptides; D019920:Photoaffinity Labels; D051722:ADAM Proteins; D000072196:Fertilins; D008666:Metalloendopeptidases