Glial Cell Line-Derived Neurotrophic Factor Requires Transforming Growth Factor-β for Exerting Its Full Neurotrophic Potential on Peripheral and CNS Neurons
作者： Kerstin Krieglstein , Prisca Henheik , Lilla Farkas , Jozsef Jaszai , Dagmar Galter
DOI: 10.1523/JNEUROSCI.18-23-09822.1998
关键词:
摘要: Numerous studies have suggested that glial cell line-derived neurotrophic factor (GDNF) is a potent molecule. We show now on variety of cultured neurons including peripheral autonomic, sensory, and CNS dopaminergic GDNF not trophically active unless supplemented with TGF-beta. Immunoneutralization endogenous TGF-beta provided by serum or TGF-beta-secreting cells, as e.g., neurons, in culture abolishes the effect GDNF. The dose-response relationship required for synergistic identifies 60 pg/ml either combined 2 ng/ml other EC50. GDNF/TGF-beta signaling employs activation phosphatidylinositol-3 (PI-3) kinase an intermediate step shown specific PI-3 inhibitor wortmannin. action involves protection glycosylphosphatidylinositol (GPI)-linked receptors restoration their trophic effects after phosphatidylinositol-specific phospholipase C-mediated hydrolysis GPI-anchored family receptor alpha. biological significance synergism underscored colocalization all investigated GDNF-responsive neuron populations vivo. Moreover, vivo relevance TGF-beta/GDNF highlighted co-storage secretory vesicles model neuron, chromaffin cell, activity-dependent release. Our results broaden definition incorporating possibility two factors lack activity when acting separately become concert. our data may substantial impact treatment neurodegenerative diseases.
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