GDNF and GFRα1 promote formation of neuronal synapses by ligand-induced cell adhesion
GDNF and GFRα1 promote formation of neuronal synapses by ligand-induced cell adhesion
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DOI：
10.1038/nn1855
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发表时间：
2007-03-01
影响因子：
25
通讯作者：
Ibanez, Carlos F.
中科院分区：
文献类型：
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作者：
Ledda, Fernanda;Paratcha, Gustavo;Ibanez, Carlos F.
突触连接的建立需要突触前和突触后末端的精确对准。胶质细胞系衍生的神经营养因子 (GDNF) 受体 GFR α 1 在海马神经元的突触前和突触后区室中富集，表明它在突触形成中具有功能。 GDNF 触发 GFR α 1 分子之间的反式同质结合以及 GFR α 1 表达细胞之间的细胞粘附。这是由配体诱导的细胞粘附分子（LICAM）介导的细胞间相互作用的第一个例子。在 GDNF 存在的情况下，异位 GFR α 1 诱导海马神经元局部突触前分化，如通过囊泡蛋白和神经递质转运蛋白的聚集以及活性依赖性囊泡回收所显示的那样。在缺乏 GFR α 1 的神经元中，GDNF 诱导的突触前分化显着减少。Gdnf 突变小鼠表现出突触前蛋白的突触定位减少，突触前斑点密度显着降低，表明 GDNF 信号在体内海马突触发生中的作用。我们提出 GFR α 1 作为 LICAM 发挥作用，建立精确的突触接触并诱导突触前分化。
The establishment of synaptic connections requires precise alignment of pre- and postsynaptic terminals. The glial cell line derived neurotrophic factor (GDNF) receptor GFR alpha 1 is enriched at pre- and postsynaptic compartments in hippocampal neurons, suggesting that it has a function in synapse formation. GDNF triggered trans-homophilic binding between GFR alpha 1 molecules and cell adhesion between GFR alpha 1-expressing cells. This represents the first example of a cell-cell interaction being mediated by a ligand-induced cell adhesion molecule (LICAM). In the presence of GDNF, ectopic GFR alpha 1 induced localized presynaptic differentiation in hippocampal neurons, as visualized by clustering of vesicular proteins and neurotransmitter transporters, and by activity-dependent vesicle recycling. Presynaptic differentiation induced by GDNF was markedly reduced in neurons lacking GFR alpha 1. Gdnf mutant mice showed reduced synaptic localization of presynaptic proteins and a marked decrease in the density of presynaptic puncta, indicating a role for GDNF signaling in hippocampal synaptogenesis in vivo. We propose that GFR alpha 1 functions as a LICAM to establish precise synaptic contacts and induce presynaptic differentiation.