Cdk-mediated phosphorylation of the Kvβ2 auxiliary subunit regulates Kv1 channel axonal targeting.
Cdk-mediated phosphorylation of the Kvβ2 auxiliary subunit regulates Kv1 channel axonal targeting.
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DOI：
10.1083/jcb.201007113
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发表时间：
2011-03-07
期刊：
影响因子：
--
通讯作者：
Trimmer JS
中科院分区：
文献类型：
--
作者：
Vacher H;Yang JW;Cerda O;Autillo-Touati A;Dargent B;Trimmer JS
Kv1 β2的磷酸化释放微管中的Kv1通道，以控制其在轴突膜上的特定分布。Kv1通道集中在轴突膜的特定部位，在那里它们调节神经元的兴奋性。建立这些分布需要调节Kv1通道与神经元运输机制的分离，并随后插入轴突膜。我们发现从脑中纯化的Kv1通道的辅助Kvβ2亚基在丝氨酸残基9和31上被磷酸化，并且细胞周期蛋白依赖性激酶（Cdk）介导的磷酸化在这些位点负调控Kvβ2与微管加末端跟踪蛋白EB1的相互作用。在丝氨酸31位点磷酸化的内源性Cdks、EB1和Kvβ2共定位于培养海马神经元的轴突，并在轴突初始段（AIS）富集。Cdk活性的急性抑制导致AIS内EB1、Kvβ2和Kv1通道亚基的细胞内积累。这些研究揭示了一种新的调控机制，通过可逆的Cdk磷酸化依赖的Kv1 β2与EB1的结合，将Kv1复合物靶向轴突膜。
Phosphorylation of Kvβ2 releases Kv1 channels from microtubules to control their specific distribution at the axonal membrane. Kv1 channels are concentrated at specific sites in the axonal membrane, where they regulate neuronal excitability. Establishing these distributions requires regulated dissociation of Kv1 channels from the neuronal trafficking machinery and their subsequent insertion into the axonal membrane. We find that the auxiliary Kvβ2 subunit of Kv1 channels purified from brain is phosphorylated on serine residues 9 and 31, and that cyclin-dependent kinase (Cdk)–mediated phosphorylation at these sites negatively regulates the interaction of Kvβ2 with the microtubule plus end–tracking protein EB1. Endogenous Cdks, EB1, and Kvβ2 phosphorylated at serine 31 are colocalized in the axons of cultured hippocampal neurons, with enrichment at the axon initial segment (AIS). Acute inhibition of Cdk activity leads to intracellular accumulation of EB1, Kvβ2, and Kv1 channel subunits within the AIS. These studies reveal a new regulatory mechanism for the targeting of Kv1 complexes to the axonal membrane through the reversible Cdk phosphorylation-dependent binding of Kvβ2 to EB1.
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DOI：
10.1083/jcb.200805169
发表时间：
2008-12-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bréchet A;Fache MP;Brachet A;Ferracci G;Baude A;Irondelle M;Pereira S;Leterrier C;Dargent B
通讯作者：
Dargent B
影响因子：
21.3
作者：
Guillaud, Laurent;Wong, Richard;Hirokawa, Nobutaka
通讯作者：
Hirokawa, Nobutaka
影响因子：
14.5
作者：
Jen, J. C.;Graves, T. D.;Baloh, R. W.
通讯作者：
Baloh, R. W.
影响因子：
16.2
作者：
Adelman, JP;Bond, CT;Maylie, J
通讯作者：
Maylie, J
影响因子：
56.9
作者：
Long, SB;Campbell, EB;MacKinnon, R
通讯作者：
MacKinnon, R