Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Glypicans (GPCs)

  • Jorge FilmusEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101637


 Glypican-1: Glypican; Glypican 1; Glypican-1; GPC1

 Glypican-2: Glypican 2; Glypican-2; GPC2; Cerebroglycan

 Glypican-3: Glypican 3; Glypican-3; GPC3; MXR7; OCI-5

 Glypican-4: Glypican 4; Glypican-4; GPC4; K-glypican

 Glypican-5: Glypican 5; Glypican-5; GPC5

 Glypican-6: Glypican 6; Glypican-6; GPC6

Historical Background

Glypican-3 (GPC3) is the first glypican that was cloned (Filmus et al. 1988). Initially named OCI-5, GPC3 was identified in 1988 as a gene whose expression was developmentally regulated in the intestine. Two years later, the cloning of Glypican-1 (GPC1) was reported. This report characterized GPC1 as a glycosylphosphatidylinositol (GPI)-anchored heparan sulfate proteoglycan (HSPG), but it did not indicate that GPC1 displays significantly homology with GPC3 (David et al. 1990). This homology was noticed 4 years later in a study that reported the cloning of Glypican-2 (initially called cerebroglycan) (Stipp et al. 1994). This study established for the first...

This is a preview of subscription content, log in to check access.


  1. Allen NJ, Bennett ML, Foo LC, Wang GX, Chakraborty C, Smith SJ, et al. Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature. 2012;486:410–4.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Campos-Xavier AB, Martinet D, Bateman J, Belluocio D, Rowley L, Tan TY, et al. Mutations in the heparan-sulfate proteoglycan glypican-6 (GPC6) impair endochodral ossification and cause recessive omodysplasia. Am J Hum Genet. 2009;84:760–70.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Capurro MI, Xu P, Shi W, Li F, Jia A, Filmus J. Glypican-3 inhibits hedgehog signaling during development by competing with patched for Hedgehog binding. Dev Cell. 2008;14:700–11.PubMedCrossRefGoogle Scholar
  5. David G, Lories V, Decock B, Marynen P, Cassiman J, Van Den Berghe H. Molecular cloning of a phosphatidylinositol-anchored membrane heparan sulfate proteoglycan from human lung fibroblasts. J Cell Biol. 1990;111:3165–76.PubMedCrossRefGoogle Scholar
  6. Filmus J, Capurro M. Glypican-3: a marker and a therapeutic target in hepatocellular carcinoma. FEBS J. 2013;280:2471–6.PubMedCrossRefGoogle Scholar
  7. Filmus J, Capurro M. The role of glypicans in Hedgehog signaling. Matrix Biol. 2014;35:248–52.PubMedCrossRefGoogle Scholar
  8. Filmus J, Church JG, Buick RN. Isolation of a cDNA corresponding to a developmentally regulated transcript in rat intestine. Mol Cell Biol. 1988;8:4243–9.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Filmus J, Capurro M, Rast J. Glypicans. Genome Biol. 2008;9:224.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Gao W, Tang Z, Zhang YF, Feng M, Qian M, Dimitrov DS, et al. Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis. Nat Commun. 2015;6:6536.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Jackson SM, Nakato H, Sugiura M, Jannuzi A, Oakes R, Kaluza V, et al. dally, a Drosophila glypican, controls celular responses to the TGF-beta-related morphogen Dpp. Development. 1997;124:4113–20.PubMedGoogle Scholar
  12. Ko JS, Pramanik G, Um JW, Shim JS, Lee D, Kim KH, et al. PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission. Proc Natl Acad Sci USA. 2015;112:1874–9.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Li F, Shi W, Capurro M, Filmus J. Glypican-5 stimulates rhabdomyosarcoma cell proliferation by activating Hedgehog signaling. J Cell Biol. 2011;192:691–704.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Lin X, Perrimon N. Dally cooperates with Drosophila Frizzled 2 to transduce wingless signaling. Nature. 1999;400:281–4.PubMedCrossRefGoogle Scholar
  15. Lum L, Yao S, Mozer B, Rovescalli A, Von Kessler D, Nirenberg M, et al. Identification of hedgehog pathway components by RNAi in Drosophila cultured cells. Science. 2003;299:2039–45.PubMedCrossRefGoogle Scholar
  16. Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015;523:177–82.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Nakato H, Futch TA, Selleck SB. The division abnormally delayed (dally) gene: a putative integral membrane proteoglycan required for cell division patterning during postembryonic development of the nervous system in Drosophila. Development. 1995;121:3687–702.PubMedGoogle Scholar
  18. Okamoto K, Tokunaga K, Doi K, Fujita T, Suzuki H, Katoh T, et al. Common variation in GPC5 is associated with acquired nephrotic syndrome. Nat Genet. 2011;43:459–63.PubMedCrossRefGoogle Scholar
  19. Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, et al. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 1996;12:241–7.PubMedCrossRefGoogle Scholar
  20. Song YS, Kim E. Presynaptic proteoglycans: sweet organizers of synapse development. Neuron. 2013;79:609–11.PubMedCrossRefGoogle Scholar
  21. Stipp CS, Litwac ED, Lander AD. Cerebroglycan: an integral membrane heparan sulfate proteoglycan that is unique to the developing nervous system and expressed specifically during neuronal differentiation. J Cell Biol. 1994;124:149–60.PubMedCrossRefGoogle Scholar
  22. Svensson G, Awad W, Hakansson M, Mani K, Logan DT. Crystal structure of N-glycosylated human glypican-1 core protein: structure of two loops evolutionary conserved in vertebrate glypican-1. J Biol Chem. 2012;287:14040–51.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Wilson NH, Stoeckli ET. Sonic hedgehog regulates its own receptor on postcrossing commissural axons in a glypican1-dependent manner. Neuron. 2013;79:478–91.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Sunnybrook Research InstituteUniversity of TorontoTorontoCanada