Abstract
A family of multidomain membrane proteins, the ADAM family (a disintegrin and metalloprotease), comprises at least 32 members. Based on an ADAM phylogenetic tree, mammalian ADAMs with testis-specific or -predominant expression are divided into two major groups: ADAMs 1, 4, 6, 20, 21, 24, 25, 26, 29, 30 and 34 (the first group), and ADAMs 2, 3, 5, 27 and 32 (the second group). All of the mammalian, testicular ADAMs predicted as active metalloproteases (ADAMs 1, 20, 21, 24, 25, 26, 30 and 34) belong to the first phylogenetic group and are unique in several aspects. All of these ADAM genes lack introns in their coding sequences and many of them are present as multiple copies in the mouse genome, resulting in total of 11 functional genes (ADAMs 1a, 1b, 21, 24, 25a, 25b, 25c, 26a, 26b, 30 and 34) predicted to encode active proteases. These genes are transcribed by both somatic and germ cells with higher expression level in post-meiotic germ cells in the testis. The ADAM 1 protein expressed in testicular germ cells is complexed with ADAM 2 to form a heterodimer and processed during spermatogenesis. Mouse knockout studies indicate that ADAM 1a/2 heterodimer in testicular germ cells is implicated in the regulation or localization of sperm proteins involved in sperm progression in the female reproductive tract, sperm penetration into the cumulus cell layer and sperm-egg zona pellucida binding, thus playing a central role in fertilization. ADAM 24 is a potential sperm protease implicated in sperm function during sperm maturation or fertilization. A number of the 11 mouse ADAMs do not have orthologues in human and, even if they exist, some orthologues are pseudogenes in human. As a result, only 3 human ADAMs (ADAMs 20, 21 and 30) are functional genes encoding potential metalloproteases. Uncovering the in vivo functions of the testicular ADAM proteases present in both species should provide insights into the mammalian reproductive system involving protease-mediated events.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Almeida, E.A., Huovila, A.P., Sutherland, A.E., Stephens, L.E., Calarco, P.G., Shaw, L.M., Mercurio, A.M., Sonnenberg, A., Primakoff, P., Myles, D.G., White, J.M., 1995,. Mouse egg integrin α6β1 functions as a sperm receptor. Cell 81: 1095–1104.
Blobel, C.P., Myles, D.G., Primakoff, P., White, J.M., 1990, Proteolytic processing of a protein involved in sperm-egg fusion correlates with acquisition of fertilization competence. J. Cell Biol. 111: 69–78.
Blobel, C.P., Wolfsberg, T.G., Turck, C.W., Myles, D.G., Primakoff, P., White, J.M., 1992, A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion. Nature 356: 248–252.
Blobel, C.P., 1997, Metalloprotease-disintegrins: links to cell adhesion and cleavage of TNF alpha and Notch. Cell 90: 589–592.
Blobel, C.P., 2000, Functional processing of fertilin: evidence for a critical role of proteolysis in sperm maturation and activation. Rev. Reprod. 5: 75–83.
Black, R.A., White. J.M., 1998, ADAMs: focus on the protease domain. Curr. Opin. Cell Biol. 10: 654–659.
Bolcun, E., Rzymski, T., Nayernia, K., Engel, W., 2003, ADAM family genes testase 2 α and 2 β are chromosomally linked and simultaneously expressed in male germ cells. Mol. Reprod. Dev. 65: 19–22.
Brachvogel, B., Reichenberg, D., Beyer, S., Jehn, B., von der Mark, K., Bielke, W., 2002, Molecular cloning and expression analysis of a novel member of the Disintegrin and Metalloprotease-Domain (ADAM) family. Gene 288: 203–210.
Cerretti, D.P., DuBose, R.F., Black, R.A., Nelson, N., 1999, Isolation of two novel metalloproteinase-disintegrin (ADAM) cDNAs that show testis-specific gene expression. Biochem. Biophys. Res. Commun. 263: 810–815.
Cho, C., Primakoff, P., White, J.M., Myles, D.G., 1996, Chromosomal assignment of four testis-expressed mouse genes from a new family of transmembrane proteins (ADAMs) involved in cell-cell adhesion and fusion. Genomics 34: 413–417.
Cho, C., Turner, L., Primakoff, P., Myles, D.G., 1997, Genomic organization of the mouse fertilin β gene that encodes an ADAM family protein active in sperm-egg fusion. Dev. Genet. 20: 320–328.
Cho, C., Bunch D.O., Faure, J.-E., Goulding E.H., Eddy, E.M., Primakoff, P., Myles, D.G., 1998, Fertilization defects in sperm from mice lacking fertilin β. Science 281: 1857–1859.
Cho, C., Ge, H., Branciforte, D., Primakoff, P., Myles, D.G., 2000, Analysis of mouse fertilin in wild-type and fertilin β-/- sperm: evidence for C-terminal modification, α/β dimerization, and lack of essential role of fertilin α in sperm-egg fusion. Dev. Biol. 222:289–295.
Choi, I., Woo, J.M., Hong, S., Jung, Y.K., Kim D.H., Cho, C., 2003, Identification and characterization of ADAM32 with testis-predominant gene expression. Gene 304: 151–162.
Choi, I., Oh, J., Cho, B.N., Ahnn, J., Jung, Y.K., Kim H.D., Cho, C., 2004, Characterization and comparative genomic analysis of intronless Adams with testicular gene expression. Genomics 83: 636–646.
Eddy, E.M., 1998, Regulation of gene expression during spermatogenesis, Semin. Cell Dev. Biol. 9: 451–457.
Evans, J.P., Schultz, R.M., Kopf, G.S., 1995, Mouse sperm-egg plasma membrane interactions: analysis of roles of egg integrins and the mouse sperm homologue of PH-30 (fertilin) β. J. Cell Sci. 108: 3267–3278.
Evans J.P., Schultz, R.M., Kopf, G.S., 1998, Roles of the disintegrin domains of mouse fertilins α and β in fertilization. Biol. Reprod. 59: 145–152.
Evans, J.P., 2001, Fertilin β and other ADAMs as integrin ligands: insights into cell adhesion and fertilization. Bioessays 23: 628–639.
Frayne, J., Jury, J.A., Barker, H.L., Hall, L., 1997, Rat MDC family of proteins: sequence analysis, tissue distribution, and expression in prepubertal and adult rat testis. Mol. Reprod. Dev. 48: 159–167.
Frayne, J., Jury, J.A., Barker, H.L., Perry, A.C., Jones, R., Hall, L., 1998, Macaque MDC family of proteins: sequence analysis, tissue distribution and processing in the male reproductive tract. Mol. Hum. Reprod. 4: 429–437.
Hardy, C.M., Holland, M.K.,1996, Cloning and expression of recombinant rabbit fertilin. Mol Reprod. Dev. 45: 107–116.
Hooft van Huijsduijnen, R., 1998, ADAM 20 and 21; two novel human testis-specific membrane metalloproteases with similarity to fertilin-α. Gene 206: 273–282.
Hunnicutt, G.R., Koppel, D.E., Myles, D.G., 1997, Analysis of the process of localization of fertilin to the sperm posterior head plasma membrane domain during sperm maturation in the epididymis. Dev. Biol. 191: 146–159.
Ikawa, M., Wada, I., Kominami, K., Watanabe, D., Toshimori, K., Nishimune, Y., Okabe, M., 1997, The putative chaperone calmegin is required for sperm fertility. Nature 387: 607–611.
Ikawa, M., Nakanishi, T., Yamada, S., Wada, I., Kominami, K., Tanaka, H., Nozaki, M., Nishimune, Y., Okabe, M., 2001, Calmegin is required for fertilin α/β heterodimerization and sperm fertility. Dev Biol. 240: 254–261.
Jury, J.A., Frayne, J., Hall, L., 1997, The human fertilin α gene is non-functional: implications for its proposed role in fertilization. Biochem. J. 321: 577–581.
Jury, J.A., Frayne, J., Hall, L., 1998, Sequence analysis of a variety of primate fertilin α genes: evidence for non-functional genes in the gorilla and man. Mol. Reprod. Dev. 51:92–97.
Kim, E., Nishimura, H., Baba, T., 2003, Differential localization of ADAM1a and ADAM1b in the endoplasmic reticulum of testicular germ cells and on the surface of epididymal sperm. Biochem. Biophys. Res. Commun. 304: 313–319.
Liu, L., Smith, J.W., 2000, Identification of ADAM 31: a protein expressed in Leydig cells and specialized epithelia. Endocrinology 141: 2033–2042.
Lum, L., Blobel, C.P., 1997, Evidence for distinct serine protease activities with a potential role in processing the sperm protein fertilin. Dev Biol. 191: 131–145.
Martin, I., Epand, R.M., Ruysschaert, J.M., 1998, Structural properties of the putative fusion peptide of fertilin, a protein active in sperm-egg fusion, upon interaction with the lipid bilayer. Biochemistry 37: 17030–17039.
McLaughlin, E.A., Frayne, J., Barker, H.L., Jury, J.A., Jones, R., Ford, W.C., Hall, L., 1997, Cloning and sequence analysis of rat fertilin α and β-developmental expression, processing and immunolocalization. Mol. Hum. Reprod. 3: 801–809.
Muga, A., Neugebauer, W., Hirama, T., Surewicz, W.K., 1994, Membrane interactive and conformational properties of the putative fusion peptide of PH-30, a protein active in sperm-egg fusion. Biochemistry 33: 4444–4448.
Myles, D.G., 1993, Molecular mechanisms of sperm-egg membrane binding and fusion in mammals. Dev. Biol. 158: 35–45.
Myles, D.G., Kimmel, L.H., Blobel, C.P., White, J.M., Primakoff, P., 1994, Identification of a binding site in the disintegrin domain of fertilin required for sperm-egg fusion. Proc. Natl. Acad. Sci. U.S.A. 91: 4195–4198.
Myles, D.G., Primakoff, P., 1997, Why did the sperm cross the cumulus? To get to the oocyte. Functions of the sperm surface proteins PH-20 and fertilin in arriving at, and fusing with, the egg. Biol. Reprod. 56: 320–327.
Niidome, T., Kimura, M., Chiba, T., Ohmori, N., Mihara, H., Aoyagi, H., 1997, Membrane interaction of synthetic peptides related to the putative fusogenic region of PH-30α, a protein in sperm-egg fusion. J. Pept. Res. 49: 563–569.
Nishimura, H., Cho, C., Branciforte, D.R., Myles, D.G., Primakoff, P., 2001, Analysis of loss of adhesive function in sperm lacking cyritestin or fertilin β. Dev. Biol. 233: 204–213.
Nishimura, H., Kim, E., Fujimori, T., Kashiwabara, S., Kuroiwa, A., Matsuda, Y., Baba, T., 2002, The ADAM1a and ADAM1b genes, instead of the ADAM1 (fertilin α) gene, are localized on mouse chromosome 5. Gene 291: 67–76.
Nishimura, H., Kim, E., Nakanishi, T., Baba, T., 2004, Possible function of the ADAM1a/ADAM2 fertilin complex in the appearance of ADAM3 on the sperm surface. J. Biol. Chem. in press.
Perry, A.C., Jones, R., Hall, L., 1995, Analysis of transcripts encoding novel members of the mammalian metalloprotease-like, disintegrin-like, cysteine-rich (MDC) protein family and their expression in reproductive and non-reproductive monkey tissues. Biochem. J. 312:239–244.
Phelps, B.M., Koppel, D.E., Primakoff, P., Myles, D.G., 1990, Evidence that proteolysis of the surface is an initial step in the mechanism of formation of sperm cell surface domains. J. Cell Biol. 111: 1839–1847.
Poindexter, K., Nelson, N, DuBose, R.F., Black, R.A., Cerretti, D.P, 1999, The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries. Gene 237:61–70.
Primakoff, P., Hyatt, H., Tredick-Kline, J., 1989, Identification and purification of a sperm surface protein with a potential role in sperm-egg membrane fusion. J. Cell Biol. 104: 141–149.
Primakoff, P., Myles, D.G., 2000, The ADAM gene family. Trends Genet. 16: 83–87.
Primakoff, P., Myles, D.G., 2002, Penetration, adhesion, and fusion in mammalian sperm-egg interaction. Science 296: 2183–2185.
Puente, X.S., Sanchez, L.M., Overall, C.M., Lopez-Otin, C., 2003, Human and mouse proteases: a comparative genomic approach. Nat. Rev. Genet. 4: 544–558.
Shamsadin., R., Adham, I.M., Nayernia, K., Heinlein, U.A., Oberwinkler, H., Engel, W., 1999, Male mice deficient for germ-cell cyritestin are infertile. Biol. Reprod. 61: 1445–1451.
Snell, W.J., White, J.M., 1996, The molecules of mammalian fertilization. Cell 85: 629–637.
Talbot, P., Shur, B.D., Myles, D.G., 2003, Cell adhesion and fertilization: steps in oocyte transport, sperm-zona pellucida interactions, and sperm-egg fusion. Biol. Reprod. 68: 1–9.
Wassarman, P.M., 1999, Mammalian fertilization: molecular aspects of gamete adhesion, exocytosis, and fusion. Cell 96: 175–183.
Waters, S.I., White, J.M., 1997, Biochemical and molecular characterization of bovine fertilin α and β (ADAM 1 and ADAM 2): a candidate sperm-egg binding/fusion complex. Biol. Reprod. 56: 1245–1254.
Waterston, R.H. et al., 2002, Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562.
White, J.M., 2003, ADAMs: modulators of cell-cell and cell-matrix interactions. Curr. Opin. Cell Biol. 15: 598–606.
Wolfe, C.A., Cladera, J., Ladha, S., Senior, S., Jones, R., O’Shea, P., 1999, Membrane interactions of the putative fusion peptide (MF αP) from fertilin-α, the mouse sperm protein complex involved in fertilization. Mol. Membr. Biol. 16: 257–263.
Wolfsberg, T.G., Bazan, J.F., Blobel, C.P., Myles, D.G., Primakoff, P., White, J.M., 1993, The precursor region of a protein active in sperm-egg fusion contains a metalloprotease and a disintegrin domain: structural, functional, and evolutionary implications. Proc. Natl. Acad. Sci. U.S.A. 90: 10783–10787.
Wolfsberg, T.G., Primakoff, P., Myles, D.G., White, J.M., 1995a, ADAM, a novel family of membrane proteins containing A Disintegrin And Metalloprotease domain: multipotential functions in cell-cell and cell-matrix interactions. J. Cell Biol. 131: 275–278.
Wolfsberg, T.G., Straight, P.D., Gerena, R.L., Huovila, A.-P.J., Primakoff, P., Myles, D.G., White, J.M., 1995b, ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with A Disintegrin And Metalloprotease domain. Dev. Biol. 169: 378–383.
Wolfsberg, T.G., White, J.M., 1996, ADAMs in fertilization and development. Dev. Biol. 180: 389–401.
Wong, G.E., Zhu, X., Prater, C.E., Oh, E., Evans, J.P., 2001, Analysis of fertilin α (ADAM1)-mediated sperm-egg cell adhesion during fertilization and identification of an adhesion-mediating sequence in the disintegrin-like domain. J. Biol. Chem. 276: 24937–24945.
Yanagimachi, R., 1994, Mammalian fertilization. In: The Physiology of Reproduction. Knobil E and Neill JD Eds. Raven, New York, pp189–317.
Yuan, R., Primakoff, P., Myles, D.G., 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. J. Cell Biol. 137: 105–112.
Zhu, G.-Z., Lin, Y., Myles, D.G., Primakoff, O., 1999, Identification of four novel ADAMs with potential roles in spermatogenesis and fertilization. Gene 234: 227–237.
Zhu, G.-Z., Myles, D.G., Primakoff, P., 2001, Testase 1 (ADAM24) a plasma membrane-anchored sperm protease implicated in sperm function during epididymal maturation or fertilization. J. Cell Sci. 114: 1787–1794.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer
About this chapter
Cite this chapter
Cho, C. (2005). Mammalian ADAMs with Testis-Specific or -Predominant Expression. In: Hooper, N.M., Lendeckel, U. (eds) The ADAM Family of Proteases. Proteases in Biology and Disease, vol 4. Springer, Boston, MA. https://doi.org/10.1007/0-387-25151-0_11
Download citation
DOI: https://doi.org/10.1007/0-387-25151-0_11
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-25149-3
Online ISBN: 978-0-387-25151-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)