Nerve Growth Factor-induced Glutamate Release Is via p75 Receptor, Ceramide, and Ca2+ from Ryanodine Receptor in Developing Cerebellar Neurons*

Nerve Growth Factor-induced Glutamate Release Is via p75 Receptor, Ceramide, and Ca2+ from Ryanodine Receptor in Developing Cerebellar Neurons*
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神经生长因子诱导的谷氨酸释放是通过小脑神经元发育过程中的 p75 受体、神经酰胺和 Ryanodine 受体中的 Ca2 实现的*

DOI:
10.1074/jbc.m304409200
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发表时间:
2003
影响因子:
4.8
通讯作者:
T. Taguchi
T. Taguchi
中科院分区:
生物学2区
文献类型:
--
作者:
T. Numakawa;H. Nakayama;Shingo Suzuki;T. Kubo;F. Nara;Yumiko Numakawa;D. Yokomaku;T. Araki;T. Ishimoto;A. Ogura;T. Taguchi

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Very little is known about the contribution of a low affinity neurotrophin receptor, p75, to neurotransmitter release. Here we show that nerve growth factor (NGF) induced a rapid release of glutamate and an increase of Ca2+ in cerebellar neurons through a p75-dependent pathway. The NGF-induced release occurred even in the presence of the Trk inhibitor K252a. The release caused by NGF but not brain-derived neurotrophic factor was enhanced in neurons overexpressing p75. Further, after transfection of p75-small interfering RNA, which down-regulated the endogenous p75 expression, the NGF-induced release was inhibited, suggesting that the NGF-induced glutamate release was through p75. We found that the NGF-increased Ca2+ was derived from the ryanodine-sensitive Ca2+ receptor and that the NGF-increased Ca2+ was essential for the NGF-induced glutamate release. Furthermore, scyphostatin, a sphingomyelinase inhibitor, blocked the NGF-dependent Ca2+ increase and glutamate release, suggesting that a ceramide produced by sphingomyelinase was required for the NGF-stimulated Ca2+ increase and glutamate release. This action of NGF only occurred in developing neurons whereas the brain-derived neurotrophic factor-mediated Ca2+ increase and glutamate release was observed at the mature neuronal stage. Thus, we demonstrate that NGF-mediated neurotransmitter release via the p75-dependent pathway has an important role in developing neurons.
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DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
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