The Kvβ2 subunit of voltage-gated potassium channels is interacting with ProSAP2/Shank3 in the PSD
The Kvβ2 subunit of voltage-gated potassium channels is interacting with ProSAP2/Shank3 in the PSD
复制标题
电压门控钾通道的 Kvβ2 亚基与 PSD 中的 ProSAP2/Shank3 相互作用
DOI：
10.1016/j.neuroscience.2013.10.045
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发表时间：
2014
期刊：
影响因子：
3.3
通讯作者：
Liebau St
中科院分区：
文献类型：
--
作者：
Proepper C;Putz St;Boeckers TM;Liebau St
突触后密度是由多种分子组成的电子密集网络，促进神经元信号的传递。ProSAP2/Shank3在突触后位点发挥关键作用，组装大的多聚体平台并锚定许多其他分子，从而将功能性突触与细胞骨架连接起来。ProSAP2/Shank3也与许多疾病的发病机制有关，包括自闭症谱系障碍。另一方面，KvBeta2 （Kvβ2）作为电压门控钾通道的调节亚基。Kvβ2位于神经元的各个部位，包括轴突（与Kv1.2结合）、树突（与Kv4.2结合）和突触。与Kv1.2或Kv4结合的Kvβ2不仅可以调节通道构象，还可以将通道蛋白复合物定向到细胞内不同的位点。因此，ProSAP2和Kvβ2之间的相互作用可能在不同的细胞区室和成熟阶段发挥重要作用。我们在这里报道了突触后密度锚定分子ProSAP2和钾通道亚基Kvβ2的直接蛋白-蛋白相互作用，最初是在酵母-双杂交筛选中发现的。此外，我们表征这种相互作用在突触使用初级海马神经元体外。
The postsynaptic density is an electron dense meshwork composed of a variety of molecules facilitating neuronal signal transmission. ProSAP2/Shank3 represents a crucial player at postsynaptic sites, assembling large multimeric platforms and anchoring numerous other molecules, thereby linking the functional synapse with the cytoskeleton. ProSAP2/Shank3 is also implicated in the pathogenesis of numerous diseases, including autism spectrum disorders. KvBeta2 (Kvβ2) on the other hand serves as a regulatory subunit of voltage-gated potassium channels. Kvβ2 is located at various sites in the neuron including the axon (binding to Kv1.2), the dendrites (binding to Kv4.2) and the synapse. Binding of Kvβ2 to either Kv1.2 or Kv4 modulates not only the channel conformation but directs targeting of the channel protein complex to distinct loci within the cell. Thus an interaction between ProSAP2 and Kvβ2 could have important roles at diverse cellular compartments and moreover during maturation stages. We report here on the direct protein–protein interaction of the postsynaptic density anchoring molecule ProSAP2 and the potassium channel subunit Kvβ2, initially identified in a yeast-two-hybrid-screen. Furthermore, we characterize this interaction at synapses using primary hippocampal neuronsin vitro.