Neuroglycan C is a novel midkine receptor involved in process elongation of oligodendroglial precursor-like cells

J Biol Chem. 2006 Oct 13;281(41):30857-64. doi: 10.1074/jbc.M602228200. Epub 2006 Aug 10.


Midkine is a heparin-binding growth factor that promotes cell attachment and process extension in undifferentiated bipolar CG-4 cells, an oligodendroglial precursor cell line. We found that CG-4 cells expressed a non-proteoglycan form of neuroglycan C, known as a part-time transmembrane proteoglycan. We demonstrated that neuroglycan C before or after chondroitinase ABC treatment bound to a midkine affinity column. Neuroglycan C lacking chondroitin sulfate chains was eluted with 0.5 m NaCl as a major fraction from the column. We confirmed that CG-4 cells expressed two isoforms of neuroglycan C, I, and III, by isolating cDNA. Among three functional domains of the extracellular part of neuroglycan C, the chondroitin sulfate attachment domain and acidic amino acid cluster box domain showed affinity for midkine, but the epidermal growth factor domain did not. Furthermore, cell surface neuroglycan C could be cross-linked with soluble midkine. Process extension on midkine-coated dishes was inhibited by either a monoclonal anti-neuroglycan C antibody C1 or a glutathione S-transferase-neuroglycan C fusion protein. Finally, stable transfectants of B104 neuroblastoma cells overexpressing neuroglycan C-I or neuroglycan C-III attached to the midkine substrate, spread well, and gave rise to cytoskeletal changes. Based on these results, we conclude that neuroglycan C is a novel component of midkine receptors involved in process elongation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Chondroitin ABC Lyase / metabolism
  • Chondroitin Sulfate Proteoglycans / chemistry
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Chondroitin Sulfate Proteoglycans / physiology*
  • Chondroitin Sulfates / chemistry
  • Cytokines / metabolism
  • Epidermal Growth Factor / chemistry
  • Humans
  • Mice
  • Midkine
  • Neuregulins / chemistry
  • Neuregulins / metabolism
  • Neuregulins / physiology*
  • Oligodendroglia / metabolism*
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Rats


  • Chondroitin Sulfate Proteoglycans
  • Cytokines
  • Neuregulins
  • Protein Isoforms
  • neuroglycan C, human
  • Midkine
  • Epidermal Growth Factor
  • Chondroitin Sulfates
  • Chondroitin ABC Lyase