Skip to main content

Advertisement

Log in

Neuroglycan C, A Brain-Specific Chondroitin Sulfate Proteoglycan, Interacts with Pleiotrophin, A Heparin-Binding Growth Factor

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Neuroglycan C (NGC) is a transmembrane-type chondroitin sulfate proteoglycan that promotes neurite outgrowth. To identify the ligand of NGC, we applied a detergent-solubilized membrane fraction of fetal rat brains to an NGC-immobilized affinity column. Several proteins were eluted from the column including an 18 kDa-band protein recognized by an anti-pleiotrophin antibody. The binding of pleiotrophin (PTN) to NGC was confirmed by a quartz crystal microbalance method and had a Kd of 8.7 nM. PTN bound to the acidic amino acid cluster of the NGC extracellular domain. In addition, PTN bound to both chondroitin sulfate-bearing NGC and chondroitinase-treated NGC prepared from the neonatal rat brain. These results suggest that NGC interacts with PTN.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Watanabe E, Maeda N, Matsui F et al (1995) Neuroglycan C, a novel membrane-spanning chondroitin sulfate proteoglycan that is restricted to the brain. J Biol Chem 270:26876–26882

    Article  PubMed  CAS  Google Scholar 

  2. Oohira A, Shuo T, Tokita Y et al (2004) Neuroglycan C, a brain-specific part-time proteoglycan, with a particular multidomain structure. Glycoconj J 21:53–57

    Article  PubMed  CAS  Google Scholar 

  3. Schumacher S, Volkmer H, Buck F et al (1997) Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB), a neural member of the EGF family of differentiation factors, is implicated in neurite formation. J Cell Biol 136:895–906

    Article  PubMed  CAS  Google Scholar 

  4. Nakanishi K, Aono S, Hirano K et al (2006) Identification of neurite outgrowth-promoting domains of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, and involvement of phosphatodylinositol 3-kinase and protein kinase C signaling pathways. J Biol Chem 281:24970–24978

    Article  PubMed  CAS  Google Scholar 

  5. Brandt N, Franke K, Rasin MR et al (2007) The neural EGF family member CALEB/NGC mediates dendritic tree and spine complexity. EMBO J 26:2371–2386

    Article  PubMed  CAS  Google Scholar 

  6. Ichihara-Tanaka K, Oohira A, Rumsby M et al (2006) Neuroglycan C is a novel midkine receptor involved in process elongation of oligodendroglial precursor-like cells. J Biol Chem 281:30857–30864

    Article  PubMed  CAS  Google Scholar 

  7. Aono S, Tokita Y, Yasuda Y et al (2006) Expression and identification of a new splice variant of neuroglycan C (NGC), a transmembrane chondroitin sulfate proteoglycan, in the human brain. J Neurosci Res 83:110–118

    Article  PubMed  CAS  Google Scholar 

  8. Shuo T, Aono S, Nakanishi K et al (2007) Ectodomain shedding of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, by TIMP-2- and TIMP-3-sensitive proteolysis. J Neurochem 102:1561–1568

    Article  PubMed  CAS  Google Scholar 

  9. Shuo T, Aono S, Matsui F et al (2004) Developmental changes in the biochemical and immunological characters of the carbohydrate moiety of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan. Glycoconj J 20:267–278

    Article  PubMed  CAS  Google Scholar 

  10. Sato Y, Sagami I, Shimizu T (2004) Identification of caveolin-1-interacting sites in neuronal nitric-oxide synthase. J Biol Chem 279:8827–8836

    Article  PubMed  CAS  Google Scholar 

  11. Oohira A, Matsui F, Watanabe E et al (1994) Developmentally regulated expression of a brain specific species of chondroitin sulfate proteoglycan, neurocan, identified with a monoclonal antibody 1G2 in the rat cerebrum. Neuroscience 60:145–157

    Article  PubMed  CAS  Google Scholar 

  12. Schumacher S, Jung M, Nörenberg U et al (2001) CALEB binds via its acidic stretch to the fibrinogen-like domain of tenascin-C or tenascin-R and its expression is dynamically regulated after optic nerve lesion. J Biol Chem 276:7337–7345

    Article  PubMed  CAS  Google Scholar 

  13. Merenmies J, Pihlaskari R, Laitinen J et al (1991) 30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. J Biol Chem 266:16722–16729

    PubMed  CAS  Google Scholar 

  14. Keino H, Kawashima S (2000) Amphoterin in rat cerebellar development. Zool Sci 17(suppl):106

    Google Scholar 

  15. Aono S, Tokita Y, Shuo T et al (2004) Glycosylation site for chondroitin sulfate on the neural part-time proteoglycan, neuroglycan C. J Biol Chem 279:46536–46541

    Article  PubMed  CAS  Google Scholar 

  16. Rauvala H (1989) An 18-kd heparin-binding protein of developing brain that is distinct from fibroblast growth factors. EMBO J 8:2933–2941

    PubMed  CAS  Google Scholar 

  17. Raulo E, Chernousov MA, Carey DJ et al (1994) Isolation of a neuronal cell surface receptor of heparin binding growth-associated molecule (HB-GAM). J Biol Chem 269:12999–13004

    PubMed  CAS  Google Scholar 

  18. Maeda N, Nishiwaki T, Shintani T et al (1996) 6B4 proteoglycan phosphacan, an extracellular variant of receptor-like protein-tyrosine phosphatase ζ/RPTPβ, binds pleiotrophin/heparin-binding growth-associated molecule (HB-GAM). J Biol Chem 271:21446–21452

    Article  PubMed  CAS  Google Scholar 

  19. Hienola A, Tumova S, Kulesskiy E et al (2006) N-syndecan deficiency impairs neural migration in brain. J Cell Biol 174:569–580

    Article  PubMed  CAS  Google Scholar 

  20. Maeda N, Noda M (1998) Involvement of receptor-like protein tyrosine phosphataseζ/RPTPβ and its ligand pleiotrophin/heparin-binding growth-associated molecule (HB-GAM) in neuronal migration. J Cell Biol 142:203–216

    Article  PubMed  CAS  Google Scholar 

  21. Stoica GE, Kuo A, Aigner A et al (2001) Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin. J Biol Chem 276:16772–16779

    Article  PubMed  CAS  Google Scholar 

  22. Siri A, Knäuper V, Veirana N et al (1995) Different susceptibility of small and large human tenascin-C isoform to degradation by matrix metalloproteinases. J Biol Chem 270:8650–8654

    Article  PubMed  CAS  Google Scholar 

  23. Pesheva P, Probstmeier R (2000) Association of tenscin-R with murine brain myelin membranes: involvement of divalent cations. Neurosci Lett 283:165–168

    Article  PubMed  CAS  Google Scholar 

  24. Kaneda N, Talukder AH, Nishiyama H et al (1996) Midkine, a heparin-binding growth/differentiation factor, exhibits nerve cell adhesion and guidance activity for neurite outgrowth in vitro. J Biochem (Tokyo) 119:1150–1156

    CAS  Google Scholar 

  25. Dai LC, Wang X, Yao X et al (2007) Antisense oligonucleotide targeting midkine suppresses in vivo angiogenesis. World J Gastroenterol 13:1208–1213

    PubMed  CAS  Google Scholar 

  26. Zhang N, Zhong R, Wang Z-Y et al (1997) Human breast cancer growth inhibited in vivo by a dominant negative pleiotrophin mutant. J Biol Chem 272:16733–16736

    Article  PubMed  CAS  Google Scholar 

  27. Muramatsu T (2002) Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis. J Biochem 132:359–371

    PubMed  CAS  Google Scholar 

  28. Kadomatsu K (2005) The midkine family in cancer, inflammation and neural development. Nagoya J Med Sci 67:71–82

    PubMed  CAS  Google Scholar 

  29. Perez-Pinera P, Berenson JR, Deuel TF (2008) Pleiotrophin, a multifunctional angiogenic factor: mechanisms and pathways in normal and pathological angiogenesis. Curr Opin Hematol 15:210–214

    Article  PubMed  CAS  Google Scholar 

  30. Zou P, Muramatsu H, Miyata T et al (2006) Midkine, a heparin-binding growth factor, is expressed in neural precursor cells and promotes their growth. J Neurochem 99:1470–1479

    Article  PubMed  CAS  Google Scholar 

  31. Hienola A, Pekkanen M, Raulo E et al (2004) HB-GAM inhibits proliferation and enhances differentiation of neural stem cells. Mol Cell Neurosci 26:75–88

    Article  PubMed  CAS  Google Scholar 

  32. Ida M, Shuo T, Hirano K et al (2006) Identification and functions of chondroitin sulfate in the milieu of neural stem cells. J Biol Chem 281:5982–5991

    Article  PubMed  CAS  Google Scholar 

  33. Matsumoto K, Wanaka A, Takatsuji K et al (1994) A novel family of heparin-binding growth factors, pleiotrophin and midkine, is expressed in the developing rat cerebral cortex. Dev Brain Res 79:229–241

    Article  CAS  Google Scholar 

  34. Amet LE, Lauri SE, Hienola A et al (2001) Enhanced hippocampal long-term potentiation in mice lacking heparin-binding growth-associated molecule. Mol Cell Neurosci 17:1014–1024

    Article  PubMed  CAS  Google Scholar 

  35. Lauri SE, Rauvala H, Kaila K et al (1998) Effect of heparin-binding growth-associated molecule (HB-GAM) on synaptic transmission and early LTP in rat hippocampal slices. Eur J Neurosci 10:188–194

    Article  PubMed  CAS  Google Scholar 

  36. del Olmo N, Gramage E, Alguacil LF et al (2009) Pleiotrophin inhibits hippocampal long-term potentiation: a role of pleiotrophin in learning and memory. Growth Factors 27:189–194

    Article  PubMed  CAS  Google Scholar 

  37. Jüttner R, Moré MI, Das D et al (2005) Impaired synapse function during postnatal development in the absence of CALEB, an EGF-like protein processed by neural activity. Neuron 46:233–245

    Article  PubMed  CAS  Google Scholar 

  38. Muller D, Toni N, Buchs PA (2000) Spine changes associated with long-term potentiation. Hippocampus 10:596–604

    Article  PubMed  CAS  Google Scholar 

  39. Carlisle HJ, Kennedy MB (2005) Spine architecture and synaptic plasticity. Trends Neurosci 28:182–187

    Article  PubMed  CAS  Google Scholar 

  40. Deepa SS, Umehara Y, Higashiyama S et al (2002) Specific molecular interactions of oversulfated chondroitin sulfate E with various heparin-binding growth factors. J Biol Chem 277:43707–43716

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank to Dr. M. Watanabe (Aichi Human Service Center) for his helpful discussions. The present study was supported in part by Grants-in-aid for Scientific Research from the Ministry of Education, Science, Culture and Sports of Japan, and from the Japan Society for the Promotion of Science.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Keiko Nakanishi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakanishi, K., Tokita, Y., Aono, S. et al. Neuroglycan C, A Brain-Specific Chondroitin Sulfate Proteoglycan, Interacts with Pleiotrophin, A Heparin-Binding Growth Factor. Neurochem Res 35, 1131–1137 (2010). https://doi.org/10.1007/s11064-010-0164-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-010-0164-9

Keywords

Navigation