Ca2+ binding protein frequenin mediates GDNF-induced potentiation of Ca2+ channels and transmitter release

被引:99
作者
Wang, CY
Yang, F
He, XP
Chow, A
Du, J
Russell, JT
Lu, B [1 ]
机构
[1] NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA
[2] George Washington Univ, Grad Program Genet, Washington, DC 20052 USA
关键词
D O I
10.1016/S0896-6273(01)00434-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Molecular mechanisms underlying long-term neurotrophic regulation of synaptic transmission and plasticity are unknown. We report here that long-term treatment of neuromuscular synapses with glial cell line-derived neurotrophic factor (GDNF) potentiates spontaneous and evoked transmitter release, in ways very similar to presynaptic expression of the Ca2+ binding protein frequenin. GDNF enhances the expression of frequenin in motoneurons, and inhibition of frequenin expression or activity prevents the synaptic action of GDNF. GDNF also facilitates Ca2+ influx into the nerve terminals during evoked transmission by enhancing Ca2+ currents. The effect of GDNF on Ca2+ currents is blocked by inhibition of frequenin expression, occluded by overexpression of frequenin, and is selective to N-type Ca2+ channels. These results identify an important molecular target that mediates the long-term, synaptic action of a neurotrophic factor.
引用
收藏
页码:99 / 112
页数:14
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