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Gene Review

Gpc1  -  glypican 1

Rattus norvegicus

Synonyms: Glypican-1, HSPG M12, HSPGM12
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Disease relevance of Gpc1


High impact information on Gpc1

  • In contrast, ES does not inhibit epidermal growth factor-dependent morphogenesis in renal epithelial cells derived from Gpc-3 -/mice, whereas expression of Gpc-1 in these cells reconstitutes ES responsiveness [4].
  • Neuronal expression of glypican, a cell-surface glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan, in the adult rat nervous system [5].
  • Comparison of the results with protein sequence predicted by a cDNA cloned from PC12 cells indicated that M12 is rat glypican, a proteoglycan first cloned from human fibroblasts [5].
  • In most cases where glypican hybridization was observed, the signal could be localized specifically to the cell bodies of identifiable neurons, for example, spinal motoneurons, hippocampal pyramidal cells [5].
  • In the cerebral cortex, glypican hybridization was found in layers 2/3, 5, and 6, but was missing from 1 and 4 [5].

Chemical compound and disease context of Gpc1


Biological context of Gpc1

  • This study demonstrates that FSH, through its second messengers (increase in intracellular cAMP and intracellular calcium), downregulated the glypican-1 mRNA expression in Sertoli cells from 20-day-old rats [6].
  • Visualization of basic fibroblast growth factor binding sites by means of a tissue slice overlay assay also revealed colocalization with glypican [7].
  • Glypican-1 is coexpressed with robo 2 and its up-regulation after axonal injury may contribute to an altered sensitivity to axonal growth or guidance cues [3].
  • The deduced amino acid sequence and the 3'- and 5'-untranslated sequences have 89% and 66-80% identity, respectively, with those of a phosphatidylinositol-anchored human lung fibroblast heparan sulfate proteoglycan (glypican) for which mRNA is detectable in a large number of human cell lines [8].
  • By using a novel quantitative approach for assessing proteoglycan glycosylation, we show here that removal of the globular domain from rat glypican-1 converts the proteoglycan from one that bears approximately 90% heparan sulfate (HS) to one that bears approximately 90% chondroitin sulfate [9].

Anatomical context of Gpc1


Associations of Gpc1 with chemical compounds

  • Heparan sulfate proteoglycans as adhesive and anti-invasive molecules. Syndecans and glypican have distinct functions [11].
  • In cell-free experiments, the presence of free Zn(II) ions prevented free Cu(II) ion from binding to glypican-1 and precluded extensive heparan sulfate autodegradation [1].
  • However, in the presence of Cu(II)-loaded ceruloplasmin, heparan sulfate in Zn(II)-loaded glypican-1 underwent extensive, ascorbate-induced degradation [1].
  • Despite distinct molecular masses of glypican and syndecan glycosaminoglycans and minor differences in disaccharide composition and sulfation pattern, the overall proportion and distribution of sulfated regions and the affinity for the Hep II domain were similar [12].
  • Interestingly, the heparan sulfate-bearing proteoglycans glypican-1 and beta glycan fail to concentrate in uropods, indicating that targeting may require heparan sulfate structural motifs unique to syndecan-1 or that the core protein of syndecan-1 participates in specific interactions that promote heparan sulfate-mediated targeting [13].

Regulatory relationships of Gpc1


Other interactions of Gpc1

  • Surprisingly, cells bearing a chimera composed of the glypican extracellular domain fused to the syndecan transmembrane and cytoplasmic domains bind to collagen but remain invasive, implying that adhesion to collagen is not by itself sufficient to inhibit invasion [11].
  • Heparan sulfate chains from glypican and syndecans bind the Hep II domain of fibronectin similarly despite minor structural differences [12].
  • In adult heart syndecan-3 and glypican mRNAs were abundantly expressed [7].
  • Syndecans (1-4), glypican, and cerebroglycan are membrane-associated HSPGs that have been implicated in these events in various tissues and several tumor cell lines [10].
  • Specifically, the level of expression of syndecan-2 and -4 and glypican mRNAs increased as the cells differentiated from proliferative late progenitors to postmitotic mature cells [10].

Analytical, diagnostic and therapeutic context of Gpc1


  1. Involvement of glycosylphosphatidylinositol-linked ceruloplasmin in the copper/zinc-nitric oxide-dependent degradation of glypican-1 heparan sulfate in rat C6 glioma cells. Mani, K., Cheng, F., Havsmark, B., David, S., Fransson, L.A. J. Biol. Chem. (2004) [Pubmed]
  2. Immunocytochemical and in situ hybridization studies of the heparan sulfate proteoglycan, glypican, in nervous tissue. Karthikeyan, L., Flad, M., Engel, M., Meyer-Puttlitz, B., Margolis, R.U., Margolis, R.K. J. Cell. Sci. (1994) [Pubmed]
  3. Dynamic changes in glypican-1 expression in dorsal root ganglion neurons after peripheral and central axonal injury. Bloechlinger, S., Karchewski, L.A., Woolf, C.J. Eur. J. Neurosci. (2004) [Pubmed]
  4. Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud. Karihaloo, A., Karumanchi, S.A., Barasch, J., Jha, V., Nickel, C.H., Yang, J., Grisaru, S., Bush, K.T., Nigam, S., Rosenblum, N.D., Sukhatme, V.P., Cantley, L.G. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  5. Neuronal expression of glypican, a cell-surface glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan, in the adult rat nervous system. Litwack, E.D., Stipp, C.S., Kumbasar, A., Lander, A.D. J. Neurosci. (1994) [Pubmed]
  6. Regulation of glypican-1, syndecan-1 and syndecan-4 mRNAs expression by follicle-stimulating hormone, cAMP increase and calcium influx during rat Sertoli cell development. Brucato, S., Bocquet, J., Villers, C. Eur. J. Biochem. (2002) [Pubmed]
  7. Developmental and cell-type-specific expression of cell surface heparan sulfate proteoglycans in the rat heart. Asundi, V.K., Keister, B.F., Stahl, R.C., Carey, D.J. Exp. Cell Res. (1997) [Pubmed]
  8. Cloning of a major heparan sulfate proteoglycan from brain and identification as the rat form of glypican. Karthikeyan, L., Maurel, P., Rauch, U., Margolis, R.K., Margolis, R.U. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  9. Mechanisms underlying preferential assembly of heparan sulfate on glypican-1. Chen, R.L., Lander, A.D. J. Biol. Chem. (2001) [Pubmed]
  10. Developmental and FGF-2-mediated regulation of syndecans (1-4) and glypican in oligodendrocytes. Bansal, R., Kumar, M., Murray, K., Pfeiffer, S.E. Mol. Cell. Neurosci. (1996) [Pubmed]
  11. Heparan sulfate proteoglycans as adhesive and anti-invasive molecules. Syndecans and glypican have distinct functions. Liu, W., Litwack, E.D., Stanley, M.J., Langford, J.K., Lander, A.D., Sanderson, R.D. J. Biol. Chem. (1998) [Pubmed]
  12. Heparan sulfate chains from glypican and syndecans bind the Hep II domain of fibronectin similarly despite minor structural differences. Tumova, S., Woods, A., Couchman, J.R. J. Biol. Chem. (2000) [Pubmed]
  13. Heparan sulfate regulates targeting of syndecan-1 to a functional domain on the cell surface. Yang, Y., Børset, M., Langford, J.K., Sanderson, R.D. J. Biol. Chem. (2003) [Pubmed]
  14. Similarities and differences between the effects of heparin and glypican-1 on the bioactivity of acidic fibroblast growth factor and the keratinocyte growth factor. Berman, B., Ostrovsky, O., Shlissel, M., Lang, T., Regan, D., Vlodavsky, I., Ishai-Michaeli, R., Ron, D. J. Biol. Chem. (1999) [Pubmed]
  15. Role of glypican-1 in the trophic activity on PC12 cells induced by cultured sciatic nerve conditioned medium: identification of a glypican-1-neuregulin complex. Malavé, C., Villegas, G.M., Hernández, M., Martínez, J.C., Castillo, C., Suárez de Mata, Z., Villegas, R. Brain Res. (2003) [Pubmed]
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