Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract??? Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side chains from heparan sulfate proteoglycans (HSPGs) present in extracellular matrix and cell membranes. Although HSPGs have many functions during development, little is known of the role of the enzyme that degrades HS, heparanase. We cloned and characterized the expression of two heparanase splicing variants from Xenopus laevis and studied their function in early embryonic development. The heparanase gene (termed xHpa) spans over 15 kb and consists of at least 12 exons. The long heparanase (XHpaL) cDNA encodes a 531-amino acid protein, whereas the short splicing variant (XHpaS) results in a protein with the same open reading frame but missing 58 amino acids as a consequence of a skipped exon 4. Comparative studies of both isoforms using heterologous expression systems showed: 1) XHpaL is enzymatically active, whereas XHpaS is not; 2) XHpaL and XHpaS interact with heparin and HS; 3) both proteins traffic through the endoplasmic reticulum and Golgi apparatus, but XHpaL is secreted into the medium, whereas XHpaS remains associated with the membrane as a consequence of the loss of three glycosylation sites; 4) overexpression of XHpaS but not XHpaL increases cell adhesion of glioma cells to HS-coated surfaces; 5) XHpaL and XHpaS mRNA and protein levels vary as development progresses; 6) specific antisense knock-down of both XHpaL and XHpaS, but not XHpaL alone, results in failure of embryogenesis to proceed. Interestingly, rescue experiments suggest that the two heparanases regulate the same developmental processes, but via different mechanisms.
Abboud-Jarrous,
Site-directed mutagenesis, proteolytic cleavage, and activation of human proheparanase.
2005, Pubmed
Abboud-Jarrous,
Site-directed mutagenesis, proteolytic cleavage, and activation of human proheparanase.
2005,
Pubmed
Allen,
Spatial and temporal expression of heparan sulfate in mouse development regulates FGF and FGF receptor assembly.
2003,
Pubmed
Aviezer,
Differential structural requirements of heparin and heparan sulfate proteoglycans that promote binding of basic fibroblast growth factor to its receptor.
1994,
Pubmed
Bartlett,
Comparative analysis of the ability of leucocytes, endothelial cells and platelets to degrade the subendothelial basement membrane: evidence for cytokine dependence and detection of a novel sulfatase.
1995,
Pubmed
Bellaiche,
Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion.
1998,
Pubmed
Ben-Zaken,
Heparanase induces Akt phosphorylation via a lipid raft receptor.
2007,
Pubmed
Binari,
Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling.
1997,
Pubmed
Casu,
Structure and biological interactions of heparin and heparan sulfate.
2001,
Pubmed
Dong,
Genomic organization and chromosome localization of the newly identified human heparanase gene.
2000,
Pubmed
Galli,
Glypican 4 modulates FGF signalling and regulates dorsoventral forebrain patterning in Xenopus embryos.
2003,
Pubmed
,
Xenbase
Gilat,
Molecular behavior adapts to context: heparanase functions as an extracellular matrix-degrading enzyme or as a T cell adhesion molecule, depending on the local pH.
1995,
Pubmed
Gimlich,
Early cellular interactions promote embryonic axis formation in Xenopus laevis.
1984,
Pubmed
,
Xenbase
Goldshmidt,
Heparanase mediates cell adhesion independent of its enzymatic activity.
2003,
Pubmed
Goldshmidt,
Human heparanase is localized within lysosomes in a stable form.
2002,
Pubmed
Goldshmidt,
Cell surface expression and secretion of heparanase markedly promote tumor angiogenesis and metastasis.
2002,
Pubmed
Goldshmidt,
Expression pattern and secretion of human and chicken heparanase are determined by their signal peptide sequence.
2001,
Pubmed
Goldshmidt,
Heparanase expression during normal liver development and following partial hepatectomy.
2004,
Pubmed
Häcker,
Heparan sulphate proteoglycans: the sweet side of development.
2005,
Pubmed
Hulett,
Identification of active-site residues of the pro-metastatic endoglycosidase heparanase.
2000,
Pubmed
Hulett,
Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis.
1999,
Pubmed
Johnson,
Axonal heparan sulfate proteoglycans regulate the distribution and efficiency of the repellent slit during midline axon guidance.
2004,
Pubmed
Kizaki,
Cloning and localization of heparanase in bovine placenta.
2003,
Pubmed
Kreuger,
Interactions between heparan sulfate and proteins: the concept of specificity.
2006,
Pubmed
Lennox,
Characterization of modified antisense oligonucleotides in Xenopus laevis embryos.
2006,
Pubmed
,
Xenbase
Levy-Adam,
Heterodimer formation is essential for heparanase enzymatic activity.
2003,
Pubmed
Levy-Adam,
Identification and characterization of heparin/heparan sulfate binding domains of the endoglycosidase heparanase.
2005,
Pubmed
Lindahl,
Regulated diversity of heparan sulfate.
1998,
Pubmed
McKenzie,
Biochemical characterization of the active heterodimer form of human heparanase (Hpa1) protein expressed in insect cells.
2003,
Pubmed
Miao,
Cloning, expression, and purification of mouse heparanase.
2002,
Pubmed
Moscatelli,
High and low affinity binding sites for basic fibroblast growth factor on cultured cells: absence of a role for low affinity binding in the stimulation of plasminogen activator production by bovine capillary endothelial cells.
1987,
Pubmed
Nadav,
Activation, processing and trafficking of extracellular heparanase by primary human fibroblasts.
2002,
Pubmed
Nasser,
Adaptive evolution of heparanase in hypoxia-tolerant Spalax: gene cloning and identification of a unique splice variant.
2005,
Pubmed
Nasser,
Cloning, expression, and characterization of an alternatively spliced variant of human heparanase.
2007,
Pubmed
Ohkawara,
Role of glypican 4 in the regulation of convergent extension movements during gastrulation in Xenopus laevis.
2003,
Pubmed
,
Xenbase
Parish,
Treatment of central nervous system inflammation with inhibitors of basement membrane degradation.
1998,
Pubmed
Rapraeger,
Molecular interactions of syndecans during development.
2001,
Pubmed
Revel,
Heparanase improves mouse embryo implantation.
2005,
Pubmed
Rozenberg,
Heparan sulfate, heparin, and heparinase activity detection on polyacrylamide gel electrophoresis using the fluorochrome tris(2,2'-bipyridine) ruthenium (II).
2001,
Pubmed
Shteper,
Role of promoter methylation in regulation of the mammalian heparanase gene.
2003,
Pubmed
Simizu,
Secretion of heparanase protein is regulated by glycosylation in human tumor cell lines.
2004,
Pubmed
Sindelka,
Developmental expression profiles of Xenopus laevis reference genes.
2006,
Pubmed
,
Xenbase
Sotnikov,
Enzymatically quiescent heparanase augments T cell interactions with VCAM-1 and extracellular matrix components under versatile dynamic contexts.
2004,
Pubmed
Toyoshima,
Human heparanase. Purification, characterization, cloning, and expression.
1999,
Pubmed
Vlodavsky,
Mammalian heparanase: involvement in cancer metastasis, angiogenesis and normal development.
2002,
Pubmed
Vlodavsky,
Extracellular sequestration and release of fibroblast growth factor: a regulatory mechanism?
1991,
Pubmed
Vlodavsky,
Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis.
1999,
Pubmed
Vreys,
Mammalian heparanase: what is the message?
2007,
Pubmed
Walz,
Essential role of heparan sulfates in axon navigation and targeting in the developing visual system.
1997,
Pubmed
,
Xenbase
Xu,
In vivo and in vitro degradation of heparan sulfate (HS) proteoglycans by HPR1 in pancreatic adenocarcinomas. Loss of cell surface HS suppresses fibroblast growth factor 2-mediated cell signaling and proliferation.
2007,
Pubmed
Yamane,
Molecular characterization of Xenopus embryo heparan sulfate. Differential structural requirements for the specific binding to basic fibroblast growth factor and follistatin.
1998,
Pubmed
,
Xenbase
Zcharia,
Heparanase accelerates wound angiogenesis and wound healing in mouse and rat models.
2005,
Pubmed
Zcharia,
Heparanase regulates murine hair growth.
2005,
Pubmed
Zcharia,
Transgenic expression of mammalian heparanase uncovers physiological functions of heparan sulfate in tissue morphogenesis, vascularization, and feeding behavior.
2004,
Pubmed
Zetser,
Heparanase affects adhesive and tumorigenic potential of human glioma cells.
2003,
Pubmed
