Fertility and Sterility
Volume 93, Issue 4 , Pages 1112-1123 , 1 March 2010

PCSK4-null sperm display enhanced protein tyrosine phosphorylation and ADAM2 proteolytic processing during in vitro capacitation

  • Charles Gyamera-Acheampong, M.Sc.

      Affiliations

    • Chronic Disease Program, Ottawa Health Research Institute, Ottawa, Ontario, Canada
    • Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    • ,
  • Julian Vasilescu, M.Sc.

      Affiliations

    • Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    • Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    • ,
  • Daniel Figeys, Ph.D.

      Affiliations

    • Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    • Institute of Systems Biology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    • ,
  • Majambu Mbikay, Ph.D.

      Affiliations

    • Chronic Disease Program, Ottawa Health Research Institute, Ottawa, Ontario, Canada
    • Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    • Division of Endocrinology, Ottawa Hospital, Ottawa, Ontario, Canada
    • Corresponding Author InformationReprint requests: Dr. Majambu Mbikay, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9 (FAX: 613-761-4355).

Received 8 August 2008 ,Revised 31 October 2008 ,Accepted 10 December 2008.

References 

  1. Seidah NG, Chretien M. Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res. 1999;848:45–62
  2. Seidah NG, Prat A. Precursor convertases in the secretory pathway, cytosol and extracellular milieu. Essays Biochem. 2002;38:79–94
  3. Seidah NG, Mayer G, Zaid A, Rousselet E, Nassoury N, Poirier S, et al. The activation and physiological functions of the proprotein convertases. Int J Biochem Cell Biol. 2008;40:1111–1125
  4. Seidah NG, Prat A. The proprotein convertases are potential targets in the treatment of dyslipidemia. J Mol Med. 2007;85:685–696
  5. Mbikay M, Raffin-Sanson ML, Tadros H, Sirois F, Seidah NG, Chretien M. Structure of the gene for the testis-specific proprotein convertase 4 and of its alternate messenger RNA isoforms. Genomics. 1994;20:231–237
  6. Mbikay M, Tadros H, Seidah NG, Simpson EM. Linkage mapping of the gene for the LIM-homeoprotein LIM3 (locus Lhx3) to mouse chromosome 2. Mamm Genome. 1995;6:818–819
  7. Seidah NG, Day R, Hamelin J, Gaspar A, Collard MW, Chretien M. Testicular expression of PC4 in the rat: molecular diversity of a novel germ cell-specific Kex2/subtilisin–like proprotein convertase. Mol Endocrinol. 1992;6:1559–1570
  8. Nakayama K, Kim WS, Torii S, Hosaka M, Nakagawa T, Ikemizu J, et al. Identification of the fourth member of the mammalian endoprotease family homologous to the yeast Kex2 protease. Its testis-specific expression. J Biol Chem. 1992;267:5897–5900
  9. Gyamera-Acheampong C, Tantibhedhyangkul J, Weerachatyanukul W, Tadros H, Xu H, van de Loo JW, et al. Sperm from mice genetically deficient for the PCSK4 proteinase exhibit accelerated capacitation, precocious acrosome reaction, reduced binding to egg zona pellucida, and impaired fertilizing ability. Biol Reprod. 2006;74:666–673
  10. Tadros H, Chretien M, Mbikay M. The testicular germ-cell protease PC4 is also expressed in macrophage-like cells of the ovary. J Reprod Immunol. 2001;49:133–152
  11. Nelsen S, Berg L, Wong C, Christian JL. Proprotein convertase genes in Xenopus development. Dev Dyn. 2005;233:1038–1044
  12. Qiu Q, Basak A, Mbikay M, Tsang BK, Gruslin A. Role of pro-IGF-II processing by proprotein convertase 4 in human placental development. Proc Natl Acad Sci U S A. 2005;102:11047–11052
  13. Mbikay M, Tadros H, Ishida N, Lerner CP, De Lamirande E, Chen A, et al. Impaired fertility in mice deficient for the testicular germ-cell protease PC4. Proc l Acad Sci U S A. 1997;94:6842–6846
  14. Visconti PE, Kopf GS. Regulation of protein phosphorylation during sperm capacitation. Biol Reprod. 1998;59:1–6
  15. Cho C, Bunch DO, Faure JE, Goulding EH, Eddy EM, Primakoff P, et al. Fertilization defects in sperm from mice lacking fertilin beta. Science. 1998;281:1857–1859
  16. Shamsadin R, Adham IM, Nayernia K, Heinlein UA, Oberwinkler H, Engel W. Male mice deficient for germ-cell cyritestin are infertile. Biol Reprod. 1999;61:1445–1451
  17. Nishimura H, Cho C, Branciforte DR, Myles DG, Primakoff P. Analysis of loss of adhesive function in sperm lacking cyritestin or fertilin beta. Dev Biol. 2001;233:204–213
  18. Blobel CP, Myles DG, Primakoff P, White JM. Proteolytic processing of a protein involved in sperm-egg fusion correlates with acquisition of fertilization competence. J Cell Biol. 1990;111:69–78
  19. Lum L, Blobel CP. Evidence for distinct serine protease activities with a potential role in processing the sperm protein fertilin. Dev Biol. 1997;191:131–145
  20. Tanphaichitr N, Zheng YS, Kates M, Abdullah N, Chan A. Cholesterol and phospholipid levels of washed and Percoll gradient centrifuged mouse sperm: presence of lipids possessing inhibitory effects on sperm motility. Mol Reprod Dev. 1996;43:187–195
  21. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–254
  22. Wilm M, Shevchenko A, Houthaeve T, Breit S, Schweigerer L, Fotsis T, et al. Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass spectrometry. Nature. 1996;379:466–469
  23. Moss SB, Turner RM, Burkert KL, VanScoy Butt H, Gerton GL. Conservation and function of a bovine sperm A-kinase anchor protein homologous to mouse AKAP82. Biol Reprod. 1999;61:335–342
  24. Chijiwa T, Mishima A, Hagiwara M, Sano M, Hayashi K, Inoue T, et al. Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells. J Biol Chem. 1990;265:5267–5272
  25. Colledge M, Scott JD. AKAPs: from structure to function. Trends Cell Biol. 1999;9:216–221
  26. Johnson LR, Foster JA, Haig-Ladewig L, VanScoy H, Rubin CS, Moss SB, et al. Assembly of AKAP82, a protein kinase A anchor protein, into the fibrous sheath of mouse sperm. Dev Biol. 1997;192:340–350
  27. Dong F, Ma L, Chretien M, Mbikay M. Proteomic analysis of neuroendocrine peptidergic system disruption using the AtT20 pituitary cell line as a model. Methods Mol Biol. 2008;410:111–122
  28. Luconi M, Porazzi I, Ferruzzi P, Marchiani S, Forti G, Baldi E. Tyrosine phosphorylation of the A kinase anchoring protein 3 (AKAP3) and soluble adenylate cyclase are involved in the increase of human sperm motility by bicarbonate. Biol Reprod. 2005;72:22–32
  29. Miki K, Willis WD, Brown PR, Goulding EH, Fulcher KD, Eddy EM. Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility. Dev Biol. 2002;248:331–342
  30. Kumar V, Rangaraj N, Shivaji S. Activity of pyruvate dehydrogenase A (PDHA) in hamster spermatozoa correlates positively with hyperactivation and is associated with sperm capacitation. Biol Reprod. 2006;75:767–777
  31. Evans JP. The molecular basis of sperm-oocyte membrane interactions during mammalian fertilization. Hum Reprod Update. 2002;8:297–311
  32. Linder B, Bammer S, Heinlein UA. Delayed translation and posttranslational processing of cyritestin, an integral transmembrane protein of the mouse acrosome. Exp Cell Res. 1995;221:66–72
  33. Visconti PE, Galantino-Homer H, Ning X, Moore GD, Valenzuela JP, Jorgez CJ, et al. Cholesterol efflux–mediated signal transduction in mammalian sperm. Beta-cyclodextrins initiate transmembrane signaling leading to an increase in protein tyrosine phosphorylation and capacitation. J Biol Chem. 1999;274:3235–3242
  34. Visconti PE, Ning X, Fornes MW, Alvarez JG, Stein P, Connors SA, et al. Cholesterol efflux–mediated signal transduction in mammalian sperm: cholesterol release signals an increase in protein tyrosine phosphorylation during mouse sperm capacitation. Dev Biol. 1999;214:429–443
  35. Purdy PH, Graham JK. Effect of adding cholesterol to bull sperm membranes on sperm capacitation, the acrosome reaction, and fertility. Biol Reprod. 2004;71:522–527
  36. Oliphant G, Brackett BG. Capacitation of mouse spermatozoa in media with elevated ionic strength and reversible decapacitation with epididymal extracts. Fertil Steril. 1973;24:948–955
  37. Hoppe PC. Glucose requirement for mouse sperm capacitation in vitro. Biol Reprod. 1976;15:39–45
  38. Fraser LR, Herod JE. Expression of capacitation-dependent changes in chlortetracycline fluorescence patterns in mouse spermatozoa requires a suitable glycolysable substrate. J Reprod Fertil. 1990;88:611–621
  39. Wolf DE, Hagopian SS, Ishijima S. Changes in sperm plasma membrane lipid diffusibility after hyperactivation during in vitro capacitation in the mouse. J Cell Biol. 1986;102:1372–1377
  40. Johnson WL, Hunter AG. Seminal antigens: their alteration in the genital tract of female rabbits and during partial in vitro capacitation with beta amylase and beta glucuronidase. Biol Reprod. 1972;7:332–340
  41. Talbot P, Franklin LE. Surface modification of guinea pig sperm during in vitro capacitation: an assessment using lectin-induced agglutination of living sperm. J Exp Zool. 1978;203:1–14
  42. Ho HC, Suarez SS. Hyperactivation of mammalian spermatozoa: function and regulation. Reproduction. 2001;122:519–526
  43. Zeng Y, Oberdorf JA, Florman HM. pH regulation in mouse sperm: identification of Na+-, Cl−-, and HCO3−-dependent and arylaminobenzoate-dependent regulatory mechanisms and characterization of their roles in sperm capacitation. Dev Biol. 1996;173:510–520
  44. Demarco IA, Espinosa F, Edwards J, Sosnik J, De La Vega–Beltran JL, Hockensmith JW, et al. Involvement of a Na+/HCO3− cotransporter in mouse sperm capacitation. J Biol Chem. 2003;278:7001–7009
  45. Visconti PE, Bailey JL, Moore GD, Pan D, Olds-Clarke P, Kopf GS. Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. Development. 1995;121:1129–1137
  46. Visconti PE, Moore GD, Bailey JL, Leclerc P, Connors SA, Pan D, et al. Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway. Development. 1995;121:1139–1150
  47. Lefievre L, Jha KN, de Lamirande E, Visconti PE, Gagnon C. Activation of protein kinase A during human sperm capacitation and acrosome reaction. J Androl. 2002;23:709–716
  48. Tomes CN, Roggero CM, De Blas G, Saling PM, Mayorga LS. Requirement of protein tyrosine kinase and phosphatase activities for human sperm exocytosis. Dev Biol. 2004;265:399–415
  49. Turner RM, Musse MP, Mandal A, Klotz K, Jayes FC, Herr JC, et al. Molecular genetic analysis of two human sperm fibrous sheath proteins, AKAP4 and AKAP3, in men with dysplasia of the fibrous sheath. J Androl. 2001;22:302–315
  50. Petersen C, Fuzesi L, Hoyer-Fender S. Outer dense fibre proteins from human sperm tail: molecular cloning and expression analyses of two cDNA transcripts encoding proteins of approximately 70 kDa. Mol Hum Reprod. 1999;5:627–635
  51. Mitra K, Shivaji S. Novel tyrosine-phosphorylated post-pyruvate metabolic enzyme, dihydrolipoamide dehydrogenase, involved in capacitation of hamster spermatozoa. Biol Reprod. 2004;70:887–899
  52. Li M, Mbikay M, Arimura A. Pituitary adenylate cyclase–activating polypeptide precursor is processed solely by prohormone convertase 4 in the gonads. Endocrinology. 2000;141:3723–3730
  53. Shioda S, Nakai Y, Nakajo S, Nakaya K, Arimura A. Pituitary adenylate cyclase–activating polypeptide and its type I receptors in the rat hypothalamus: neuroendocrine interactions. Ann N Y Acad Sci. 1996;805:670–676
  54. Seals DF, Courtneidge SA. The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev. 2003;17:7–30
  55. Wolfsberg TG, White JM. ADAMs in fertilization and development. Dev Biol. 1996;180:389–401
  56. Ikawa M, Wada I, Kominami K, Watanabe D, Toshimori K, Nishimune Y, et al. The putative chaperone calmegin is required for sperm fertility. Nature. 1997;387:607–611
  57. Nishimura H, Kim E, Nakanishi T, Baba T. Possible function of the ADAM1a/ADAM2 Fertilin complex in the appearance of ADAM3 on the sperm surface. J Biol Chem. 2004;279:34957–34962
  58. Bergeron F, Leduc R, Day R. Subtilase-like pro-protein convertases: from molecular specificity to therapeutic applications. J Mol Endocrinol. 2000;24:1–22
  59. Scamuffa N, Calvo F, Chretien M, Seidah NG, Khatib AM. Proprotein convertases: lessons from knockouts. Faseb J. 2006;20:1954–1963

 C.G.-A. has nothing to disclose. J.V. has nothing to disclose. D.F. has nothing to disclose. M.M. has nothing to disclose.

 Supported by the Natural Sciences and Engineering Council of Canada.

PII: S0015-0282(08)04685-2

doi: 10.1016/j.fertnstert.2008.12.013

Fertility and Sterility
Volume 93, Issue 4 , Pages 1112-1123 , 1 March 2010

Article Tools

* Image Usage & Resolution