Nerve growth factor-induced glutamate release is via p75 receptor,ceramide, and Ca(2+) from ryanodine receptor in developing cerebellar neurons |
| |
Authors: | Numakawa Tadahiro Nakayama Hitoshi Suzuki Shingo Kubo Takekazu Nara Futoshi Numakawa Yumiko Yokomaku Daisaku Araki Toshiyuki Ishimoto Tetsuya Ogura Akihiko Taguchi Takahisa |
| |
Institution: | Neuronics R G Special Division for Human Life Technology National Institute of Advanced Industrial Science and Technology (AIST) Midorigaoka, Ikeda, Osaka 563-8577, Japan. numakawa@ncnp.go.jp |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|