A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon
A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon
复制标题
DOI：
10.1523/jneurosci.4314-05.2006
复制
发表时间：
2006-03-08
影响因子：
5.3
通讯作者：
Cooper, EC
中科院分区：
文献类型：
--
作者：
Pan, ZM;Kao, TC;Cooper, EC
KCNQ（K（V）7）钾通道是阈下M电流的基础，可稳定神经元静息电位并防止动作电位的重复放电。在这里，针对四种不同的KCNQ 2和KCNQ 3多肽表位的抗体显示这些亚基集中在轴突起始段（AIS）和朗维尔结。KCNQ 2和KCNQ 3的AIS浓度与电压门控钠（Na-V）通道的AIS浓度一样，在ankrex-G基因敲除小鼠中被消除。一个短的基序，共同的KCNQ 2和KCNQ 3，介导在体内的锚-G相互作用和保留的亚基在AIS。该KCNQ 2/KCNQ 3基序与Na-V α亚基上提供这些功能的序列几乎相同。所有已鉴定的蠕虫、昆虫和软体动物的Na-V和KCNQ基因均缺乏锚定蛋白-G结合基序。相反，NaV α亚基、KCNQ 2和KCNQ 3的脊椎动物直系同源物（包括硬骨鱼、鸟类和哺乳动物）都具有该基序。因此，协同的锚定-G与KCNQ和Na-V通道的相互作用似乎是通过趋同的分子进化出现的，在无脊椎动物和脊椎动物谱系之间的划分之后，但在最后一个共同的有颌脊椎动物祖先出现之前。这包括髓鞘也进化的历史时期。
KCNQ (K(V)7) potassium channels underlie subthreshold M-currents that stabilize the neuronal resting potential and prevent repetitive firing of action potentials. Here, antibodies against four different KCNQ2 and KCNQ3 polypeptide epitopes show these subunits concentrated at the axonal initial segment (AIS) and node of Ranvier. AIS concentration of KCNQ2 and KCNQ3, like that of voltage-gated sodium (Na-V) channels, is abolished in ankyrin-G knock-out mice. A short motif, common to KCNQ2 and KCNQ3, mediates both in vivo ankyrin-G interaction and retention of the subunits at the AIS. This KCNQ2/KCNQ3 motif is nearly identical to the sequence on Na-V alpha subunits that serves these functions. All identified Na-V and KCNQ genes of worms, insects, and molluscs lack the ankyrin-G binding motif. In contrast, vertebrate orthologs of NaV alpha subunits, KCNQ2, and KCNQ3 (including from bony fish, birds, and mammals) all possess the motif. Thus, concerted ankyrin-G interaction with KCNQ and Na-V channels appears to have arisen through convergent molecular evolution, after the division between invertebrate and vertebrate lineages, but before the appearance of the last common jawed vertebrate ancestor. This includes the historical period when myelin also evolved.