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. 1993 Nov 1;90(21):10071–10075. doi: 10.1073/pnas.90.21.10071

Molecular cloning of the human and monkey sperm surface protein PH-20.

Y Lin 1, L H Kimmel 1, D G Myles 1, P Primakoff 1
PMCID: PMC47715  PMID: 8234258

Abstract

The guinea pig sperm surface protein PH-20 has an essential function in sperm adhesion to the zona pellucida of guinea pig eggs. Fully effective contraception has been achieved by immunizing either male or female guinea pigs with purified guinea pig PH-20. Here we report the isolation of human and cynomolgus monkey PH-20 cDNAs as a key step toward testing the function of primate PH-20 and the contraceptive efficacy of PH-20 immunization in primates. The deduced amino acid sequence of human PH-20 has 509 residues and is 59% identical with guinea pig PH-20, suggesting they may have a conserved function and immunogenicity. Southern blots show that there is a single PH-20 gene in the human genome and Northern blots of human testis poly(A)+ RNA show a 2.4-kb message. Northern blots of tissues other than testis are negative for PH-20, indicating that human PH-20 is testis-specific.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander N. J. Natural and induced immunological infertility. Curr Opin Immunol. 1989 Aug;1(6):1125–1130. doi: 10.1016/0952-7915(89)90003-4. [DOI] [PubMed] [Google Scholar]
  2. Bedford J. M. Sperm/egg interaction: the specificity of human spermatozoa. Anat Rec. 1977 Aug;188(4):477–487. doi: 10.1002/ar.1091880407. [DOI] [PubMed] [Google Scholar]
  3. Bronson R., Cooper G., Rosenfeld D. Sperm antibodies: their role in infertility. Fertil Steril. 1984 Aug;42(2):171–183. [PubMed] [Google Scholar]
  4. Camerini D., Seed B. A CD4 domain important for HIV-mediated syncytium formation lies outside the virus binding site. Cell. 1990 Mar 9;60(5):747–754. doi: 10.1016/0092-8674(90)90089-w. [DOI] [PubMed] [Google Scholar]
  5. Chamberlin M. E., Dean J. Human homolog of the mouse sperm receptor. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6014–6018. doi: 10.1073/pnas.87.16.6014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cowan A. E., Primakoff P., Myles D. G. Sperm exocytosis increases the amount of PH-20 antigen on the surface of guinea pig sperm. J Cell Biol. 1986 Oct;103(4):1289–1297. doi: 10.1083/jcb.103.4.1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cross G. A. Glycolipid anchoring of plasma membrane proteins. Annu Rev Cell Biol. 1990;6:1–39. doi: 10.1146/annurev.cb.06.110190.000245. [DOI] [PubMed] [Google Scholar]
  8. Goldstein L. A., Zhou D. F., Picker L. J., Minty C. N., Bargatze R. F., Ding J. F., Butcher E. C. A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell. 1989 Mar 24;56(6):1063–1072. doi: 10.1016/0092-8674(89)90639-9. [DOI] [PubMed] [Google Scholar]
  9. Kummerfeld H. L., Foote R. H. Infertility and embryonic mortality in female rabbits immunized with different sperm preparations. Biol Reprod. 1976 Apr;14(3):300–305. doi: 10.1095/biolreprod14.3.300. [DOI] [PubMed] [Google Scholar]
  10. Lathrop W. F., Carmichael E. P., Myles D. G., Primakoff P. cDNA cloning reveals the molecular structure of a sperm surface protein, PH-20, involved in sperm-egg adhesion and the wide distribution of its gene among mammals. J Cell Biol. 1990 Dec;111(6 Pt 2):2939–2949. doi: 10.1083/jcb.111.6.2939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lunsford R. D., Jenkins N. A., Kozak C. A., Liang L. F., Silan C. M., Copeland N. G., Dean J. Genomic mapping of murine Zp-2 and Zp-3, two oocyte-specific loci encoding zona pellucida proteins. Genomics. 1990 Jan;6(1):184–187. doi: 10.1016/0888-7543(90)90465-7. [DOI] [PubMed] [Google Scholar]
  12. Maddon P. J., Littman D. R., Godfrey M., Maddon D. E., Chess L., Axel R. The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell. 1985 Aug;42(1):93–104. doi: 10.1016/s0092-8674(85)80105-7. [DOI] [PubMed] [Google Scholar]
  13. Menge A. C., Peegel H., Riolo M. L. Sperm fractions responsible for immunologic induction of pre- and postfertilization infertility in rabbits. Biol Reprod. 1979 May;20(4):931–937. doi: 10.1095/biolreprod20.4.931. [DOI] [PubMed] [Google Scholar]
  14. Moller C. C., Bleil J. D., Kinloch R. A., Wassarman P. M. Structural and functional relationships between mouse and hamster zona pellucida glycoproteins. Dev Biol. 1990 Feb;137(2):276–286. doi: 10.1016/0012-1606(90)90254-g. [DOI] [PubMed] [Google Scholar]
  15. Munoz M. G., Metz C. B. Infertility in female rabbits isoimmunized with subcellular sperm fractions. Biol Reprod. 1978 May;18(4):669–678. doi: 10.1095/biolreprod18.4.669. [DOI] [PubMed] [Google Scholar]
  16. Myles D. G., Hyatt H., Primakoff P. Binding of both acrosome-intact and acrosome-reacted guinea pig sperm to the zona pellucida during in vitro fertilization. Dev Biol. 1987 Jun;121(2):559–567. doi: 10.1016/0012-1606(87)90191-6. [DOI] [PubMed] [Google Scholar]
  17. Nottenburg C., Rees G., St John T. Isolation of mouse CD44 cDNA: structural features are distinct from the primate cDNA. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8521–8525. doi: 10.1073/pnas.86.21.8521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Phelps B. M., Myles D. G. The guinea pig sperm plasma membrane protein, PH-20, reaches the surface via two transport pathways and becomes localized to a domain after an initial uniform distribution. Dev Biol. 1987 Sep;123(1):63–72. doi: 10.1016/0012-1606(87)90428-3. [DOI] [PubMed] [Google Scholar]
  19. Phelps B. M., Primakoff P., Koppel D. E., Low M. G., Myles D. G. Restricted lateral diffusion of PH-20, a PI-anchored sperm membrane protein. Science. 1988 Jun 24;240(4860):1780–1782. doi: 10.1126/science.3381102. [DOI] [PubMed] [Google Scholar]
  20. Primakoff P., Hyatt H., Myles D. G. A role for the migrating sperm surface antigen PH-20 in guinea pig sperm binding to the egg zona pellucida. J Cell Biol. 1985 Dec;101(6):2239–2244. doi: 10.1083/jcb.101.6.2239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Primakoff P., Lathrop W., Woolman L., Cowan A., Myles D. Fully effective contraception in male and female guinea pigs immunized with the sperm protein PH-20. Nature. 1988 Oct 6;335(6190):543–546. doi: 10.1038/335543a0. [DOI] [PubMed] [Google Scholar]
  22. Ringuette M. J., Chamberlin M. E., Baur A. W., Sobieski D. A., Dean J. Molecular analysis of cDNA coding for ZP3, a sperm binding protein of the mouse zona pellucida. Dev Biol. 1988 Jun;127(2):287–295. doi: 10.1016/0012-1606(88)90315-6. [DOI] [PubMed] [Google Scholar]
  23. Ringuette M. J., Sobieski D. A., Chamow S. M., Dean J. Oocyte-specific gene expression: molecular characterization of a cDNA coding for ZP-3, the sperm receptor of the mouse zona pellucida. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4341–4345. doi: 10.1073/pnas.83.12.4341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schmell E. D., Gulyas B. J. Mammalian sperm-egg recognition and binding in vitro. I. Specificity of sperm interactions with live and fixed eggs in homologous and heterologous inseminations of hamster, mouse, and guinea pig oocytes. Biol Reprod. 1980 Dec;23(5):1075–1085. doi: 10.1095/biolreprod23.5.1075. [DOI] [PubMed] [Google Scholar]
  25. Stamenkovic I., Amiot M., Pesando J. M., Seed B. A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell. 1989 Mar 24;56(6):1057–1062. doi: 10.1016/0092-8674(89)90638-7. [DOI] [PubMed] [Google Scholar]
  26. Trezise A. E., Godfrey E. A., Holmes R. S., Beacham I. R. Cloning and sequencing of cDNA encoding baboon liver alcohol dehydrogenase: evidence for a common ancestral lineage with the human alcohol dehydrogenase beta subunit and for class I ADH gene duplications predating primate radiation. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5454–5458. doi: 10.1073/pnas.86.14.5454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tung K. S., Goldberg E. H., Goldberg E. Immunobiological consequence of immunization of female mice with homologous spermatozoa: induction of infertility. J Reprod Immunol. 1979 Oct;1(3):145–158. doi: 10.1016/0165-0378(79)90015-9. [DOI] [PubMed] [Google Scholar]
  28. Wassarman P. M. Zona pellucida glycoproteins. Annu Rev Biochem. 1988;57:415–442. doi: 10.1146/annurev.bi.57.070188.002215. [DOI] [PubMed] [Google Scholar]
  29. Whitted B. E., Castle C. K., Polites H. G., Melchior G. W., Marotti K. R. Purification, cloning and nucleotide sequence determination of cynomolgus monkey apolipoprotein C-II: comparison to the human sequence. Mol Cell Biochem. 1989 Oct 5;90(1):69–79. doi: 10.1007/BF00225222. [DOI] [PubMed] [Google Scholar]
  30. von Bahr-Lindström H., Hög J. O., Hedén L. O., Kaiser R., Fleetwood L., Larsson K., Lake M., Holmquist B., Holmgren A., Hempel J. cDNA and protein structure for the alpha subunit of human liver alcohol dehydrogenase. Biochemistry. 1986 May 6;25(9):2465–2470. doi: 10.1021/bi00357a026. [DOI] [PubMed] [Google Scholar]
  31. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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