A hyaluronidase activity of the sperm plasma membrane protein PH-20 enables sperm to penetrate the cumulus cell layer surrounding the egg

doi:10.1083/jcb.125.5.1157

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A hyaluronidase activity of the sperm plasma membrane protein PH-20 enables sperm to penetrate the cumulus cell layer surrounding the egg

Y Lin, K Mahan, WF Lathrop, DG Myles and P Primakoff
Department of Physiology, University of Connecticut Health Center, Farmington 06030.

A typical mammalian egg is surrounded by an outer layer of about 3,000 cumulus cells embedded in an extracellular matrix rich in hyaluronic acid. A current, widely proposed model is that the fertilizing sperm, while it is acrosome intact, passes through the cumulus cell layer and binds to the egg zona pellucida. This current model lacks a well- supported explanation for how sperm penetrate the cumulus layer. We report that the sperm protein PH-20 has a hyaluronidase activity and is present on the plasma membrane of mouse and human sperm. Brief treatment with purified, recombinant PH-20 can release all the cumulus cells surrounding mouse eggs. Acrosome intact mouse sperm incubated with anti-PH-20 antibodies can not pass through the cumulus layer and thus can not reach the zona pellucida. These results, indicating that PH-20 enables acrosome intact sperm to penetrate the cumulus barrier, reveal a mechanism for cumulus penetration, and thus provide the missing element in the current model.
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Kim, E., Baba, D., Kimura, M., Yamashita, M., Kashiwabara, S.-i., Baba, T. (2005). Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass. Proc. Natl. Acad. Sci. USA 102: 18028-18033 [Abstract] [Full Text]
Stein, K. K., Go, J. C., Primakoff, P., Myles, D. G. (2005). Defects in Secretory Pathway Trafficking During Sperm Development in Adam2 Knockout Mice. Biol. Reprod. 73: 1032-1038 [Abstract] [Full Text]
De Jonge, C. (2005). Biological basis for human capacitation. Hum Reprod Update 11: 205-214 [Abstract] [Full Text]
Tatemoto, H., Muto, N., Yim, S.-D., Nakada, T. (2005). Anti-Hyaluronidase Oligosaccharide Derived from Chondroitin Sulfate A Effectively Reduces Polyspermy During In Vitro Fertilization of Porcine Oocytes. Biol. Reprod. 72: 127-134 [Abstract] [Full Text]
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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 [Abstract] [Full Text]
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Primakoff, P., Myles, D. G. (2002). Penetration, Adhesion, and Fusion in Mammalian Sperm-Egg Interaction. Science 296: 2183-2185 [Abstract] [Full Text]
Shuttleworth, T. L., Wilson, M. D., Wicklow, B. A., Wilkins, J. A., Triggs-Raine, B. L. (2002). Characterization of the Murine Hyaluronidase Gene Region Reveals Complex Organization and Cotranscription of Hyal1 with Downstream Genes, Fus2 and Hyal3. J. Biol. Chem. 277: 23008-23018 [Abstract] [Full Text]
Hao, Z., Wolkowicz, M. J., Shetty, J., Klotz, K., Bolling, L., Sen, B., Westbrook, V. A., Coonrod, S., Flickinger, C. J., Herr, J. C. (2002). SAMP32, a Testis-Specific, Isoantigenic Sperm Acrosomal Membrane-Associated Protein. Biol. Reprod. 66: 735-744 [Abstract] [Full Text]
Tammi, M. I., Day, A. J., Turley, E. A. (2002). Hyaluronan and Homeostasis: A Balancing Act. J. Biol. Chem. 277: 4581-4584 [Full Text]
Heldermon, C. D., Tlapak-Simmons, V. L., Baggenstoss, B. A., Weigel, P. H. (2001). Site-directed mutation of conserved cysteine residues does not inactivate the Streptococcus pyogenes hyaluronan synthase. Glycobiology 11: 1017-1024 [Abstract] [Full Text]
Rutllant, J., Meyers, S. A. (2001). Posttranslational Processing of PH-20 During Epididymal Sperm Maturation in the Horse. Biol. Reprod. 65: 1324-1331 [Abstract] [Full Text]
Zhang, H., Martin-DeLeon, P. A. (2001). Mouse Epididymal Spam1 (PH-20) Is Released In Vivo and In Vitro, and Spam1 Is Differentially Regulated in Testis and Epididymis. Biol. Reprod. 65: 1586-1593 [Abstract] [Full Text]
Lalancette, C., Dorval, V., Leblanc, V., Leclerc, P. (2001). Characterization of an 80-Kilodalton Bull Sperm Protein Identified as PH-20. Biol. Reprod. 65: 628-636 [Abstract] [Full Text]
Hammami-Hamza, S., Doussau, M., Bernard, J., Rogier, E., Duquenne, C., Richard, Y., Lefevre, A., Finaz, C. (2001). Cloning and sequencing of SOB3, a human gene coding for a sperm protein homologous to an antimicrobial protein and potentially involved in zona pellucida binding. Mol Hum Reprod 7: 625-632 [Abstract] [Full Text]
Zhu, G., Myles, D., Primakoff, P (2001). Testase 1 (ADAM 24) a plasma membrane-anchored sperm protease implicated in sperm function during epididymal maturation or fertilization. J. Cell Sci. 114: 1787-1794 [Abstract]
Seaton, G. J., Hall, L., Jones, R. (2000). Rat Sperm 2B1 Glycoprotein (PH20) Contains a C-Terminal Sequence Motif for Attachment of a Glycosyl Phosphatidylinositol Anchor. Effects of Endoproteolytic Cleavage on Hyaluronidase Activity. Biol. Reprod. 62: 1667-1676 [Abstract] [Full Text]
Meyers, S. A., Rosenberger, A. E. (1999). A Plasma Membrane-Associated Hyaluronidase Is Localized to the Posterior Acrosomal Region of Stallion Sperm and Is Associated with Spermatozoal Function. Biol. Reprod. 61: 444-451 [Abstract] [Full Text]
Lepperdinger, G., Strobl, B., Kreil, G. (1998). HYAL2, a Human Gene Expressed in Many Cells, Encodes a Lysosomal Hyaluronidase with a Novel Type of Specificity. J. Biol. Chem. 273: 22466-22470 [Abstract] [Full Text]
Jones, R, Ma, A, Hou, S., Shalgi, R, Hall, L (1996). Testicular biosynthesis and epididymal endoproteolytic processing of rat sperm surface antigen 2B1. J. Cell Sci. 109: 2561-2570 [Abstract]
Mio, K., Carrette, O., Maibach, H. I., Stern, R. (2000). Evidence That the Serum Inhibitor of Hyaluronidase May Be a Member of the Inter-alpha -inhibitor Family. J. Biol. Chem. 275: 32413-32421 [Abstract] [Full Text]