Brain-derived neurotrophic factor and neurotrophin-3 induce cell proliferation in the cochleovestibular ganglion through a glycosyl-phosphatidylinositol signaling system.
We have investigated the role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in the regulation of cell proliferation in the early developing cochleovestibular ganglion (CVG). Ganglia were isolated from 72-hr chick embryos and cultured for 24 hr. Both BDNF and NT-3 had a powerful mitogenic effect, at doses of 1-5 ng/ml, consistent with an involvement of the high-affinity receptor. Evidence for the participation of the glycosyl-phosphatidylinositol (GPI)/inositol phosphoglycan (IPG) signaling system in the mediation of proliferative effects of BDNF and NT-3 is presented. Both of these neurotrophins elicited a fast and transient hydrolysis of labeled GPI, approximately 60% in 30 sec. The dose-response profile of GPI hydrolysis overlaps the neurotrophin-induced cell proliferation response profile. Anti-IPG antibodies were able to block the growth-promoting effects of BDNF and NT-3. Anti-IPG antibodies immunoprecipitated a CVG-endogenous IPG, induced upon BDNF treatment, which exhibited proliferative stimulating properties. Both BDNF and NT-3 are proposed as potential candidates for regulation of growth during CVG development, with this mitogenic effect being mediated by the GPI/IPG signaling system.
Represa
J
J
Departamento Bioquímica, Biología Molecular y Fisiología, Facultad de Medicina, Universidad de Valladolid, Spain.
Avila
M A
MA
Romero
G
G
Mato
J M
JM
Giraldez
F
F
Varela-Nieto
I
I
D000818:Animals; D000906:Antibodies / Q000276:immunology; D019208:Brain-Derived Neurotrophic Factor; D002455:Cell Division; D002642:Chick Embryo; D003056:Cochlear Nerve / Q000166:cytology / Q000378:metabolism*; D046508:Culture Techniques; D005724:Ganglia / Q000166:cytology / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000276:immunology / Q000378:metabolism*; D007295:Inositol Phosphates / Q000276:immunology; D007700:Kinetics; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D020933:Neurotrophin 3; D011134:Polysaccharides / Q000276:immunology; D015398:Signal Transduction; D014725:Vestibular Nerve / Q000166:cytology / Q000378:metabolism*
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D017261:Glycosylphosphatidylinositols; D007295:Inositol Phosphates; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D011134:Polysaccharides; C028039:inositol phosphate glycan