A C-terminal domain directs Kv3.3 channels to dendrites
A C-terminal domain directs Kv3.3 channels to dendrites
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DOI：
10.1523/jneurosci.3672-05.2005
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发表时间：
2005-12-14
影响因子：
5.3
通讯作者：
Dunn, RJ
中科院分区：
文献类型：
--
作者：
Deng, QW;Rashid, AJ;Dunn, RJ
锥体神经元的电感觉侧线叶（ELL）的Apteronotus leptorhynchus表达Kv 3型电压门控钾通道，引起高阈值电流在体细胞和树突水平。Kv 3通道家族的两个成员AptKv3.1和AptKv3.3在这些神经元中共表达。AptKv3.3通道在四个ELL节段中的每一个中以均匀的高水平表达，而AptKv3.1通道似乎以分级的方式表达，在处理高频电感觉信号的节段中表达水平更高。免疫组织化学和重组通道表达的研究表明，这两个渠道的差异分布在ELL锥体神经元的树突。AptKv3.1集中在胞体和近端树突，而AptKv3.3分布在整个大树突树的整个范围。通过体内病毒注射的AptKv 3通道的重组通道表达允许AptKv 3亚型在体细胞树突轴上定向重靶向，揭示了负责靶向通道至远端树突的序列位于AptKv3.3蛋白的C-末端结构域内。靶向结构域包括预测结合PDZ（突触后密度-95/椎间盘大/椎间盘闭塞-1）型蛋白质-蛋白质相互作用基序的共有序列。这些发现揭示了Kv 3钾通道在感觉神经元的体细胞和树突水平上的不同功能作用是通过选择性地将Kv3.3通道分配到树突隔室的特异性靶向来实现的。
Pyramidal neurons of the electrosensory lateral line lobe (ELL) of Apteronotus leptorhynchus express Kv3-type voltage-gated potassium channels that give rise to high-threshold currents at the somatic and dendritic levels. Two members of the Kv3 channel family, AptKv3.1 and AptKv3.3, are coexpressed in these neurons. AptKv3.3 channels are expressed at uniformly high levels in each of four ELL segments, whereas AptKv3.1 channels appear to be expressed in a graded manner with higher levels of expression in segments that process high-frequency electrosensory signals. Immunohistochemical and recombinant channel expression studies show a differential distribution of these two channels in the dendrites of ELL pyramidal neurons. AptKv3.1 is concentrated in somas and proximal dendrites, whereas AptKv3.3 is distributed throughout the full extent of the large dendritic tree. Recombinant channel expression of AptKv3 channels through in vivo viral injections allowed directed retargeting of AptKv3 subtypes over the somadendritic axis, revealing that the sequence responsible for targeting channels to distal dendrites lies within the C-terminal domain of the AptKv3.3 protein. The targeting domain includes a consensus sequence predicted to bind to a PDZ (postsynaptic density-95/Discs large/zona occludens-1)-type protein-protein interaction motif. These findings reveal that different functional roles for Kv3 potassium channels at the somatic and dendritic level of a sensory neuron are attained through specific targeting that selectively distributes Kv3.3 channels to the dendritic compartment.