Role of β-catenin in synaptic vesicle localization and presynaptic assembly

Role of β-catenin in synaptic vesicle localization and presynaptic assembly
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DOI:
10.1016/s0896-6273(03)00718-9
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发表时间:
2003-11-13
期刊:
影响因子:
16.2
通讯作者:
Reichardt, LF
Reichardt, LF
中科院分区:
医学1区
文献类型:
--
作者:
Bamji, SX;Shimazu, K;Reichardt, LF

文献摘要

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钙粘蛋白和连环蛋白被认为促进大脑中突触前和突触后元件之间的粘附。在这里,我们展示了β-连环蛋白在定位突触前位点的囊泡储备池中的作用。在体内海马锥体神经元中P-连环蛋白的缺失导致每个突触的保留池囊泡的数量减少,并且对长时间重复刺激的反应受损。这对应于在培养的神经元中囊泡沿着轴突的分散。有趣的是,这些作用不是由于β-连环蛋白参与钙粘蛋白介导的粘附或wnt信号传导。相反,β-连环蛋白通过其PDZ结合结构域调节囊泡定位,以在突触处募集PDZ蛋白如Veli至钙粘蛋白。这项研究定义了一个特定的作用,钙粘蛋白和连环蛋白在突触组织超出其作用,介导细胞粘附。
Cadherins and catenins are thought to promote adhesion between pre and postsynaptic elements in the brain. Here we show a role for beta-catenin in localizing the reserved pool of vesicles at presynaptic sites. Deletion of P-catenin in hippocampal pyramidal neurons in vivo resulted in a reduction in the number of reserved pool vesicles per synapse and an impaired response to prolonged repetitive stimulation. This corresponded to a dispersion of vesicles along the axon in cultured neurons. Interestingly, these effects are not due to beta-catenin's involvement in cadherin-mediated adhesion or wnt signaling. Instead, beta-catenin modulates vesicle localization via its PDZ binding domain to recruit PDZ proteins such as Veli to cadherin at synapses. This study defines a specific role for cadherins and catenins in synapse organization beyond their roles in mediating cell adhesion.