Roles of the disintegrin domains of mouse fertilins α and β in fertilization

被引:56
作者
Evans, JP
Schultz, RM
Kopf, GS
机构
[1] Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA
关键词
D O I
10.1095/biolreprod59.1.145
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Fertilin is a heterodimer of alpha and beta subunits, both of which are members of the ADAM (A Disintegrin and A Metalloprotease domain)/MDC (Metalloprotease-Disintegrin-Cysteine-rich) family of proteins. We have previously demonstrated that recombinant forms of the putative extracellular domains of mouse fertilin alpha and fertilin beta bind to mouse eggs and inhibit sperm-egg membrane binding. In this study, we examined the roles of the disintegrin domains of fertilins alpha and beta by producing recombinant forms of fertilins alpha and beta that included the disintegrin domains (alpha DCE and beta DCE) or that were truncated so that they lack the disintegrin domains (alpha CE and beta CE) and tested the abilities of these proteins to bind to eggs and to inhibit sperm-egg binding. Fertilin beta DCE was able to inhibit sperm-egg binding, but fertilin beta CE was relatively ineffective, indicating that the disintegrin domain of fertilin beta is required for interactions with egg binding sites and/or for proper protein folding. Fertilins alpha DCE and alpha CE both inhibited sperm-egg interactions, but fertilin alpha DCE tended to be more effective. Thus, the presence of the disintegrin domain in fertilin alpha DCE apparently enhanced the ability of this recombinant protein to inhibit sperm-egg binding, either by interacting with egg binding sites or by improving the efficiency of protein folding. These data also indicate that the other domains of the fertilin a extracellular region (cysteine-rich and/or epidermal growth factor-like repeat) have the ability to block sperm binding and suggest that these domains of fertilin ex may participate in sperm-egg adhesion.
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页码:145 / 152
页数:8
相关论文
共 18 条
  • [1] MOUSE EGG INTEGRIN ALPHA-6-BETA-1 FUNCTIONS AS A SPERM RECEPTOR
    ALMEIDA, EAC
    HUOVILA, APJ
    SUTHERLAND, AE
    STEPHENS, LE
    CALARCO, PG
    SHAW, LM
    MERCURIO, AM
    SONNENBERG, A
    PRIMAKOFF, P
    MYLES, DG
    WHITE, JM
    [J]. CELL, 1995, 81 (07) : 1095 - 1104
  • [2] A model for sperm-egg binding and fusion based on ADAMs and integrins
    Bigler, D
    Chen, M
    Waters, S
    White, JM
    [J]. TRENDS IN CELL BIOLOGY, 1997, 7 (06) : 220 - 225
  • [3] A POTENTIAL FUSION PEPTIDE AND AN INTEGRIN LIGAND DOMAIN IN A PROTEIN ACTIVE IN SPERM-EGG FUSION
    BLOBEL, CP
    WOLFSBERG, TG
    TURCK, CW
    MYLES, DG
    PRIMAKOFF, P
    WHITE, JM
    [J]. NATURE, 1992, 356 (6366) : 248 - 252
  • [4] Characterization of the binding of recombinant mouse sperm fertilin alpha subunit to mouse eggs: Evidence for function as a cell adhesion molecule in sperm-egg binding
    Evans, JP
    Schultz, RM
    Kopf, GS
    [J]. DEVELOPMENTAL BIOLOGY, 1997, 187 (01) : 94 - 106
  • [5] Characterization of the binding of recombinant mouse sperm fertilin beta subunit to mouse eggs: Evidence for adhesive activity via an egg beta(1) integrin-mediated interaction
    Evans, JP
    Kopf, GS
    Schultz, RM
    [J]. DEVELOPMENTAL BIOLOGY, 1997, 187 (01) : 79 - 93
  • [6] EVANS JP, 1995, J CELL SCI, V108, P3267
  • [7] Evidence that peptides derived from the disintegrin domain of primate fertilin and containing the ECD motif block the binding of human spermatozoa to the zona-free hamster oocyte
    Gichuhi, PM
    Ford, WCL
    Hall, L
    [J]. INTERNATIONAL JOURNAL OF ANDROLOGY, 1997, 20 (03): : 165 - 170
  • [8] Examination of the immunocontraceptive potential of recombinant rabbit fertilin subunits in rabbit
    Hardy, CM
    Clarke, HG
    Nixon, B
    Grigg, JA
    Hinds, LA
    Holland, MK
    [J]. BIOLOGY OF REPRODUCTION, 1997, 57 (04) : 879 - 886
  • [9] The human fertilin alpha gene is non-functional: Implications for its proposed role in fertilization
    Jury, JA
    Frayne, J
    Hall, L
    [J]. BIOCHEMICAL JOURNAL, 1997, 321 : 577 - 581
  • [10] Evidence for distinct serine protease activities with a potential role in processing the sperm protein fertilin
    Lum, L
    Blobel, CP
    [J]. DEVELOPMENTAL BIOLOGY, 1997, 191 (01) : 131 - 145