Sperm–egg plasma membrane fusion is preceded by sperm adhesion to the egg plasma membrane. Cell–cell adhesion frequently involves multiple adhesion molecules on the adhering cells. One sperm surface protein with a role in sperm–egg plasma membrane adhesion is fertilin, a transmembrane heterodimer (α and β subunits). Fertilin α and β are the first identified members of a new family of membrane proteins that each has the following domains: pro-, metalloprotease, disintegrin, cysteine-rich, EGF-like, transmembrane, and cytoplasmic domain. This protein family has been named ADAM because all members contain a disintegrin and metalloprotease domain. Previous studies indicate that the disintegrin domain of fertilin β functions in sperm–egg adhesion leading to fusion. Full length cDNA clones have been isolated for five ADAMs expressed in mouse testis: fertilin α, fertilin β, cyritestin, ADAM 4, and ADAM 5. The presence of the disintegrin domain, a known integrin ligand, suggests that like fertilin β, other testis ADAMs could be involved in sperm adhesion to the egg membrane. We tested peptide mimetics from the predicted binding sites in the disintegrin domains of the five testis-expressed ADAMs in a sperm–egg plasma membrane adhesion and fusion assay. The active site peptide from cyritestin strongly inhibited (80–90%) sperm adhesion and fusion and was a more potent inhibitor than the fertilin β active site peptide. Antibodies generated against the active site region of either cyritestin or fertilin β also strongly inhibited (80–90%) both sperm–egg adhesion and fusion. Characterization of these two ADAM family members showed that they are both processed during sperm maturation and present on mature sperm. Indirect immunofluorescence on live, acrosome-reacted sperm using antibodies against either cyritestin or fertilin β showed staining of the equatorial region, a region of the sperm membrane that participates in the early steps of membrane fusion. Collectively, these data indicate that a second ADAM family member, cyritestin, functions with fertilin β in sperm–egg plasma membrane adhesion leading to fusion.
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7 April 1997
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April 07 1997
A Role for the Disintegrin Domain of Cyritestin, a Sperm Surface Protein Belonging to the ADAM Family, in Mouse Sperm–Egg Plasma Membrane Adhesion and Fusion
Ruiyong Yuan,
Ruiyong Yuan
*Molecular and Cellular Biology and ‡Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95616; and §Cell Biology Program, University of Connecticut Health Center, Farmington, Connecticut 06030
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Paul Primakoff,
Paul Primakoff
*Molecular and Cellular Biology and ‡Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95616; and §Cell Biology Program, University of Connecticut Health Center, Farmington, Connecticut 06030
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Diana G. Myles
Diana G. Myles
*Molecular and Cellular Biology and ‡Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95616; and §Cell Biology Program, University of Connecticut Health Center, Farmington, Connecticut 06030
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Ruiyong Yuan
*Molecular and Cellular Biology and ‡Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95616; and §Cell Biology Program, University of Connecticut Health Center, Farmington, Connecticut 06030
Paul Primakoff
*Molecular and Cellular Biology and ‡Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95616; and §Cell Biology Program, University of Connecticut Health Center, Farmington, Connecticut 06030
Diana G. Myles
*Molecular and Cellular Biology and ‡Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California 95616; and §Cell Biology Program, University of Connecticut Health Center, Farmington, Connecticut 06030
Please address all correspondence to Diana Myles, Molecular and Cellular Biology, University of California, Davis, CA 95616. Tel.: (916) 752-1553; Fax: (916) 752-3085; E-mail: [email protected]
Received:
December 17 1996
Revision Received:
January 20 1997
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1997
J Cell Biol (1997) 137 (1): 105–112.
Article history
Received:
December 17 1996
Revision Received:
January 20 1997
Citation
Ruiyong Yuan, Paul Primakoff, Diana G. Myles; A Role for the Disintegrin Domain of Cyritestin, a Sperm Surface Protein Belonging to the ADAM Family, in Mouse Sperm–Egg Plasma Membrane Adhesion and Fusion. J Cell Biol 7 April 1997; 137 (1): 105–112. doi: https://doi.org/10.1083/jcb.137.1.105
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