DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic development.
DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic development.
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DOI：
10.1038/ncomms3270
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发表时间：
2013
影响因子：
16.6
通讯作者：
Hoffman, Dax A.
中科院分区：
文献类型：
--
作者：
Lin, Lin;Sun, Wei;Throesch, Ben;Kung, Faith;Decoster, Jameice T.;Berner, Cory J.;Cheney, Richard E.;Rudy, Bernardo;Hoffman, Dax A.
二肽基肽酶6（DPP6）是Kv4介导的A型K+通道的辅助亚基，除了增强通道表面表达外，还有效地加速其动力学。DPP6基因与许多人类CNS疾病相关，包括ASD和精神分裂症。在这里，我们采用敲低和DPP6的基因缺失，以揭示其在早期神经元发育过程中的树突丝状伪足的形成和稳定的重要性。我们发现，缺乏DPP6的海马神经元在整个发育过程中和成年期表现出更稀疏的树突分支模式，沿着更少的棘。在电生理和成像实验中，我们发现，这些赤字导致更少的功能性突触和独立的钾通道亚基Kv4.2发生。我们报告说，DPP 6的胞外结构域相互作用与丝状伪足相关的肌球蛋白以及与纤维连接蛋白在细胞外基质。因此，DPP 6在细胞粘附和运动中发挥着意想不到但重要的作用，影响海马突触的发育和功能。
Dipeptidyl-peptidase 6 (DPP6) is an auxiliary subunit of Kv4-mediated A-type K+ channels that, in addition to enhancing channel surface expression, potently accelerates their kinetics. The DPP6 gene has been associated with a number of human CNS disorders including ASDs and schizophrenia. Here we employ knockdown and genetic deletion of DPP6 to reveal its importance for the formation and stability of dendritic filopodia during early neuronal development. We find that hippocampal neurons lacking DPP6 show a sparser dendritic branching pattern along with fewer spines throughout development and into adulthood. In electrophysiological and imaging experiments we show that these deficits lead to fewer functional synapses and occur independently of the potassium channel subunit Kv4.2. We report that the extracellular domain of DPP6 interacts with a filopodia-associated myosin as well as with fibronectin in the extracellular matrix. DPP6 therefore plays an unexpected but important role in cell-adhesion and motility, impacting hippocampal synaptic development and function.
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影响因子：
4.8
作者：
Homma, K;Ikebe, M
通讯作者：
Ikebe, M
影响因子：
11.2
作者：
Sato, T;Yamochi, T;Dang, NH
通讯作者：
Dang, NH
影响因子：
2.9
作者：
Nadal, Marcela S.;Amarillo, Yimy;Rudy, Bernardo
通讯作者：
Rudy, Bernardo
影响因子：
21.3
作者：
Berg, JS;Cheney, RE
通讯作者：
Cheney, RE
DOI：
10.1073/pnas.0602443103
发表时间：
2006-08-15
影响因子：
11.1
作者：
Bohil, Aparna B.;Robertson, Brian W.;Cheney, Richard E.
通讯作者：
Cheney, Richard E.