Activity- and Ca(2+)-dependent modulation of surface expression of brain-derived neurotrophic factor receptors in hippocampal neurons.
Activity- and Ca(2+)-dependent modulation of surface expression of brain-derived neurotrophic factor receptors in hippocampal neurons.
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DOI：
10.1083/jcb.150.6.1423
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发表时间：
2000-09-18
期刊：
影响因子：
--
通讯作者：
Lu B
中科院分区：
文献类型：
--
作者：
Du J;Feng L;Yang F;Lu B
脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）在中枢神经系统（central nervous system，CNS）中以活性依赖的方式调节神经元的存活和突触可塑性，但其机制尚不清楚。在这里，我们报告的BDNF受体TrkB的数量在海马神经元表面可以增加高频神经元活动和突触传递，这种作用是由Ca 2+内流介导的。使用膜蛋白生物素化以及受体结合试验，我们表明，场电刺激增加培养的海马神经元表面上的TrkB的数量。免疫荧光染色表明，电刺激促进TrkB从细胞内池移动到细胞表面，特别是在神经元突起上。表面TrkB的数量仅受高频强直刺激的调节，而不受低频刺激的调节。活动依赖性调制似乎需要Ca 2+内流，因为用电压门控Ca 2+通道或NMDA受体的阻断剂处理神经元，或去除细胞外Ca 2+，严重减弱了电刺激的作用。此外，抑制Ca 2 +/钙调蛋白依赖性激酶II（CaMKII）显着降低强直刺激的有效性。这些发现有助于我们理解神经元活动在神经营养因子功能中的作用以及受体酪氨酸激酶信号转导机制。
Brain-derived neurotrophic factor (BDNF) has been shown to regulate neuronal survival and synaptic plasticity in the central nervous system (CNS) in an activity-dependent manner, but the underlying mechanisms remain unclear. Here we report that the number of BDNF receptor TrkB on the surface of hippocampal neurons can be enhanced by high frequency neuronal activity and synaptic transmission, and this effect is mediated by Ca2+ influx. Using membrane protein biotinylation as well as receptor binding assays, we show that field electric stimulation increased the number of TrkB on the surface of cultured hippocampal neurons. Immunofluorescence staining suggests that the electric stimulation facilitated the movement of TrkB from intracellular pool to the cell surface, particularly on neuronal processes. The number of surface TrkB was regulated only by high frequency tetanic stimulation, but not by low frequency stimulation. The activity dependent modulation appears to require Ca2+ influx, since treatment of the neurons with blockers of voltage-gated Ca2+ channels or NMDA receptors, or removal of extracellular Ca2+, severely attenuated the effect of electric stimulation. Moreover, inhibition of Ca2+/calmodulin-dependent kinase II (CaMKII) significantly reduced the effectiveness of the tetanic stimulation. These findings may help us to understand the role of neuronal activity in neurotrophin function and the mechanism for receptor tyrosine kinase signaling.
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影响因子：
64.8
作者：
COHENCORY, S;FRASER, SE
通讯作者：
FRASER, SE
影响因子：
56.9
作者：
Hayashi, Y;Shi, SH;Malinow, R
通讯作者：
Malinow, R
影响因子：
4.8
作者：
Heymach, JV;Kruttgen, A;Shooter, EM
通讯作者：
Shooter, EM
DOI：
10.1016/s0169-328x(99)00015-7
发表时间：
1999-03-20
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Feng, LY;Wang, CY;Lu, B
通讯作者：
Lu, B
影响因子：
2.5
作者：
Frerking, M;Malenka, RC;Nicoll, RA
通讯作者：
Nicoll, RA