Bee venom hyaluronidase is homologous to a membrane protein of mammalian sperm.

Gmachl, Michael; Kreil, Günther

doi:10.1073/pnas.90.8.3569

Cited by 181 publications

(99 citation statements)

References 30 publications

(25 reference statements)

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“…1 are a family of enzymes that are crucial for the spread of bacterial infections, toxins present in various venoms, and possibly, cancer progression (1)(2)(3)(4)(5)(6). In humans, six HAase genes have been identified.…”

Section: Hyaluronidases (Haases)mentioning

confidence: 99%

Regulation of Hyaluronidase Activity by Alternative mRNA Splicing

Lokeshwar

Schroeder

Carey

et al. 2002

Journal of Biological Chemistry

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Hyaluronidase is a hyaluronic acid-degrading endoglycosidase that is present in many toxins and the levels of which are elevated in cancer. Hyaluronidases (HAases)1 are a family of enzymes that are crucial for the spread of bacterial infections, toxins present in various venoms, and possibly, cancer progression (1-6). In humans, six HAase genes have been identified. These genes occur in clusters of three at two chromosomal locations (Ref. 7 and human genome blast search). HYAL1, HYAL2, and HYAL3 occur on chromosome 3p21.3, and PH20, HYAL4, and HYALP1 occur on chromosome 7q31.3. With the possible exception of HYAL4 and HYALP1, all other HAases degrade hyaluronic acid (HA) (7).HA is a nonsulfated glycosaminoglycan made up of repeating disaccharide units, D-glucuronic acid, and N-acetyl-D-glucosamine. HA is present in body fluids, tissues, and the extracellular matrix (8 -10). It keeps tissues hydrated and maintains osmotic balance and cartilage integrity (8, 10). HA also actively regulates cell adhesion, migration, and proliferation by interacting with specific cell surface receptors such as CD44 and RHAMM (11). The concentrations of HA are elevated in several inflammatory diseases and various carcinomas (e.g. bladder, prostate, breast, lung, colon, and so forth; Refs. 9 and 12-19). For example, we have shown that urinary HA concentration is a highly sensitive and specific marker for detecting bladder cancer, regardless of its grade (18,19). In tumor tissues, HA may promote tumor growth and metastasis probably by actively supporting tumor cell migration and offering protection against immune surveillance (20 -22). Small fragments of HA, generated by HAases, stimulate angiogenesis (23-25). We recently showed that HA fragments of ϳ10 -15 disaccharide units stimulate endothelial cell proliferation by acting through cell surface HA receptor, RHAMM, and activating the mitogenactivated protein kinase pathway (26). We have also shown that elevated levels of HYAL1-type HAase coincide with the presence of angiogenic HA fragments in prostate tumor tissues and in the urine of bladder cancer patients (17,27).Among the six HAases, HYAL1, HYAL2, and PH20 are well characterized. HYAL1 type HAase was originally purified from human plasma and urine (28, 29). However, we have shown that HYAL1 is the major tumor-derived HAase expressed in bladder and prostate cancer tissues (17,30). It has a optimum pH range of 4.0 -4.3, and the enzyme is 50 -80% active at pH 4.5 (17). have shown that a lack of functional HYAL1 results in a disorder called mucopolysaccharidosis IX. In this study the authors identified that aa Glu 268 is crucial for HYAL1 activity. HYAL2 was originally designated as the lysosomal HAase, and it cleaves high molecular mass HA into ϳ20-kDa HA fragments (32). It has a pH optimum of ϳ4.0 and is possibly less active than other HAases. HYAL-2 may also be exposed to the cell surface through a GPI anchor (32). The third HAase gene in the 3p21.3 locus is HYAL3. Although

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Section: Hyaluronidases (Haases)mentioning

confidence: 99%

Regulation of Hyaluronidase Activity by Alternative mRNA Splicing

Lokeshwar

Schroeder

Carey

et al. 2002

Journal of Biological Chemistry

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“…Because cumulus cells are embedded in the extracellular matrix abundant in hyaluronan (11), a glycosylphosphatidylinositol (GPI)-anchored sperm hyaluronidase, PH-20, has long been believed to catalyze the hyaluronan degradation, thus enabling acrosome-intact (AI) sperm to penetrate the cumulus mass (9,(12)(13)(14)(15)(16)(17). A possible involvement of PH-20 in the binding of acrosomereacted (AR) sperm to ZP, known as secondary sperm͞ZP binding, has been also suggested (18).…”

mentioning

confidence: 99%

Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass

Kim

Baba

Kimura

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

121

171

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A glycosylphosphatidylinositol (GPI)-anchored hyaluronidase, PH-20, on the sperm surface has long been believed to assist sperm penetration through the cumulus mass surrounding the eggs. However, mouse sperm lacking PH-20 were still capable of penetrating the cumulus mass despite a delayed dispersal of cumulus cells. Intriguingly, a 55-kDa hyaluronan-hydrolyzing protein was abundantly present in wild-type and PH-20-deficient mouse sperm. In this study, we purified the 55-kDa mouse protein from soluble protein extracts released from epididymal sperm by acrosome reaction and identified as a hyaluronidase, Hyal5.

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“…In 1993, a group studying snake venom found a significant homology of hyaluronidase to PH-20 (Gmachl and Kreil, 1993). These structural data seemed to support the long-held view that hyaluronidase plays a role in fertilization.…”

Section: Sperm-egg Interactions: An Original Viewmentioning

confidence: 83%

Mechanisms of sperm-egg interactions emerging from gene-manipulated animals

Ikawa¹,

Inoue²,

Okabe³

2008

Int. J. Dev. Biol.

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Sperm-egg interactions have been studied for many years using biochemical approaches such as the employment of antibodies and ligands that interact with sperm or with eggs and their vestments. As a result, various factors that participate in fertilization have emerged. However, when animals were genetically manipulated to examine the roles of those factors, most of them were found, to our surprise, to be "not essential". Of course, all biological systems contain redundancies and compensatory mechanisms, but at least some factors were found to be "essential" after gene disruption. As a whole, the explanations of sperm-egg interactions require significant modification from the gene manipulation point of view. In this review, information about sperm-egg interactions obtained from genetically manipulated animals is mainly revisited in order to propose a new vision.

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Bee venom hyaluronidase is homologous to a membrane protein of mammalian sperm.

Cited by 181 publications

References 30 publications

Regulation of Hyaluronidase Activity by Alternative mRNA Splicing

Regulation of Hyaluronidase Activity by Alternative mRNA Splicing

Identification of a hyaluronidase, Hyal5, involved in penetration of mouse sperm through cumulus mass

Mechanisms of sperm-egg interactions emerging from gene-manipulated animals

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