Repulsion of cerebellar granule neurons by chondroitin sulfate proteoglycans is mediated by MAPK pathway.
Inhibitory molecules associated with myelin and glial scar formation inhibit axon regeneration after an injury to the central nervous system (CNS). Chondroitin sulfate proteoglycans (CSPGs) that are expressed in the scar contribute to the non-permissive properties of the CNS environment. Here, we employed a spot substrate assay and demonstrated that CSPGs have a repulsive effect on cell bodies as well as neurites of the postnatal cerebellar granule neurons (CGNs) in vitro. Through a brief inhibitor screen, we observed that the effects of CSPGs were abolished in the presence of mitogen-activated protein kinase (MAPK) inhibitor or epidermal growth factor receptor (EGFR) inhibitor. The MAPK pathway was activated in the neurons treated with CSPGs, and this activation was dependent on EGFR. Thus, CSPGs triggered the inhibition of CGNs through the activation of the EGFR-mediated MAPK pathway.
Department of Neurobiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Meika
M
Kaneko
Takekazu
T
Kubo
Katsuhiko
K
Hata
Atsushi
A
Yamaguchi
Toshihide
T
Yamashita
D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010766:Phosphorylation; D011509:Proteoglycans / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D004791:Enzyme Inhibitors; D011509:Proteoglycans; D002809:Chondroitin Sulfates; D066246:ErbB Receptors; D054460:rho-Associated Kinases; D020928:Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins