Glypican-2 binds to midkine: the role of glypican-2 in neuronal cell adhesion and neurite outgrowth.
Cell-surface heparan sulfate proteoglycans participate in molecular events that regulate cell adhesion, migration, and proliferation. The present study was performed to elucidate whether glypican-2 plays a role in interactions of neurons with midkine (MK), a heparin-binding neuroregulatory factor. MK bound to heparan sulfate chains of glypican-2 in a manner similar to syndecan-3. Microbeads coated with MK or poly-L-lysine induced clustering of glypican-2 as well as syndecan-3. Substratum-bound MK or poly-L-lysine induced cell adhesion of N2a neuroblastoma cells, while only MK promoted neurite outgrowth of these cells. Ligation of cell-surface glypican-2 with MK or an antibody against epitope-tagged glypican-2 induced cell adhesion and promoted neurite outgrowth. These results verified that cell-surface glypican-2 bound to MK and suggested that MK-glypican-2 interactions participate in neuronal cell migration and neurite outgrowth. In addition, we observed different localization of epitope-tagged glypican-2 and syndecan-3 on the surface of N2a cells; the result suggested that they may play different roles in MK-mediated neural function.
Kurosawa
N
N
Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Japan. kurosawa@eng.toyama-u.ac.jp
Chen
G Y
GY
Kadomatsu
K
K
Ikematsu
S
S
Sakuma
S
S
Muramatsu
T
T
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D002846:Chromatography, Affinity; D016207:Cytokines; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D000078792:Midkine; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009842:Oligopeptides; D010455:Peptides / Q000191:economics; D011485:Protein Binding; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D016207:Cytokines; C504454:GPC2 protein, human; D053673:Glypicans; C504456:Gpc2 protein, rat; D019812:Heparan Sulfate Proteoglycans; D008565:Membrane Proteins; D009842:Oligopeptides; D010455:Peptides; D000078792:Midkine; C085706:FLAG peptide