FGF14 N-terminal splice variants differentially modulate Nav1.2 and Nav1.6-encoded sodium channels.
FGF14 N-terminal splice variants differentially modulate Nav1.2 and Nav1.6-encoded sodium channels.
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DOI：
10.1016/j.mcn.2009.05.007
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发表时间：
2009-10
影响因子：
3.5
通讯作者：
Ornitz, David M.
中科院分区：
文献类型：
--
作者：
Laezza, Fernanda;Lampert, Angelika;Kozel, Marie A.;Gerber, Benjamin R.;Rush, Anthony M.;Nerbonne, Jeanne M.;Waxman, Stephen G.;Dib-Hajj, Sulayman D.;Ornitz, David M.
细胞内成纤维细胞生长因子（iFGF）亚家族包括结构上相关的FGF超家族的四个成员（FGF 11-14）。先前的研究表明iFGF直接与电压门控钠（Nav）通道的成孔（α）亚基相互作用并调节钠通道电流的功能特性。iFGF之间的序列异质性被认为赋予这种调节的特异性。在这里，我们证明了两个N-末端选择性剪接的FGF 14变体，FGF 14 -1a和FGF 14 -1b，差异调节Nav1.2和Nav1.6通道产生的电流。FGF 14 -1b而非FGF 14 -1a减弱Nav1.2和Nav1.6电流密度。相反，缺乏N-末端的FGF 14突变体的共表达增加了Nav1.6电流密度。在神经元中，FGF 14 -1a和FGF 14 -1b均定位于轴突起始段，N-末端的缺失消除了这种定位。因此，FGF 14 N-末端是Nav通道的靶向和功能调节所需的，表明FGF 14选择性剪接在调节神经元兴奋性中的重要功能。
The Intracellular Fibroblast Growth Factor (iFGF) subfamily includes four members (FGFs 11–14) of the structurally related FGF superfamily. Previous studies showed that the iFGFs interact directly with the pore-forming (α) subunits of voltage-gated sodium (Nav) channels and regulate the functional properties of sodium channel currents. Sequence heterogeneity among the iFGFs is thought to confer specificity to this regulation. Here, we demonstrate that the two N-terminal alternatively spliced FGF14 variants, FGF14-1a and FGF14-1b, differentially regulate currents produced by Nav1.2-and Nav1.6 channels. FGF14-1b, but not FGF14-1a, attenuates both Nav1.2 and Nav1.6 current densities. In contrast, co-expression of an FGF14 mutant, lacking the N-terminus, increased Nav1.6 current densities. In neurons, both FGF14-1a and FGF14-1b localized at the axonal initial segment, and deletion of the N-terminus abolished this localization. Thus, the FGF14 N-terminus is required for targeting and functional regulation of Nav channels, suggesting an important function for FGF14 alternative splicing in regulating neuronal excitability.
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DOI：
10.1083/jcb.200110003
发表时间：
2002-01-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komada M;Soriano P
通讯作者：
Soriano P
影响因子：
4.8
作者：
Fotia, AB;Ekberg, J;Kumar, S
通讯作者：
Kumar, S
影响因子：
5.3
作者：
Laezza, Fernanda;Gerber, Benjamin R.;Nerbonne, Jeanne M.
通讯作者：
Nerbonne, Jeanne M.
影响因子：
2.5
作者：
Levin, Stephen I.;Khaliq, Zayd M.;Meisler, Miriam H.
通讯作者：
Meisler, Miriam H.
影响因子：
16.2
作者：
Goldfarb, Mitchell;Schoorlemmer, Jon;D'Angelo, Egidio
通讯作者：
D'Angelo, Egidio