Identification of neurite outgrowth-promoting domains of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan, and involvement of phosphatidylinositol 3-kinase and protein kinase C signaling pathways in neuritogenesis.
Neuroglycan C (NGC) is a transmembrane-type chondroitin sulfate proteoglycan that is exclusively expressed in the central nervous system. We report that the recombinant ectodomain of NGC core protein enhances neurite outgrowth from rat neocortical neurons in culture. Both protein kinase C (PKC) inhibitors and phosphatidylinositol 3-kinase (PI3K) inhibitors attenuated the NGC-mediated neurite outgrowth in a dose-dependent manner, suggesting that NGC promotes neurite outgrowth via PI3K and PKC pathways. The active sites of NGC for neurite outgrowth existed in the epidermal growth factor (EGF)-like domain and acidic amino acid (AA)-domain of the NGC ectodomain. The EGF-domain caused cells to extend preferentially one neurite from a soma, whereas the AA-domain caused several neurites to develop. The EGF-domain also enhanced neurite outgrowth from GABA-positive neurons, but the AA-domain did not. These results suggest that the EGF-domain and AA-domain have distinct functions in terms of neuritogenesis. From these findings, NGC can be considered to be involved in neuritogenesis in the developing central nervous system.
Nakanishi
Keiko
K
Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan. nakanishi@inst-hsc.jp
Aono
Sachiko
S
Hirano
Kanako
K
Kuroda
Yoshiyuki
Y
Ida
Michiru
M
Tokita
Yoshihito
Y
Matsui
Fumiko
F
Oohira
Atsuhiko
A
D000818:Animals; D004815:Epidermal Growth Factor; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D019579:Neocortex / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D004815:Epidermal Growth Factor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011509:Proteoglycans; C485738:Cspg5 protein, rat