Differential characterization of three alternative spliced isoforms of DPPX
Differential characterization of three alternative spliced isoforms of DPPX
复制标题
DOI：
10.1016/j.brainres.2006.03.106
复制
发表时间：
2006-06-13
期刊：
影响因子：
2.9
通讯作者：
Rudy, Bernardo
中科院分区：
文献类型：
--
作者：
Nadal, Marcela S.;Amarillo, Yimy;Rudy, Bernardo
瞬态阈下激活体树突a型K+电流（I(SA)s）在神经元功能中起着重要作用。它们引起延迟激发，影响脉冲复极化，调节重复放电的频率，并在树突的信号处理中起重要作用。我们之前报道过DPPX蛋白是介导这些电流的通道（Kv4通道）的关键成分（bbb10, m.s., Ozaita， A., Amarillo， Y., Vega-Saenz， E., Ma， Y., Mo， W., Goldberg, e.m., Misumi， Y., Ikehara， Y., Neubert, t.a., Rudy， B., 2003）。cd26相关的二肽基氨基肽酶样蛋白DPPX是神经元a型K+通道的重要组成部分。神经元37,449-461)。DPPX基因编码选择性剪接转录物，产生具有短而分散的胞内结构域和大的胞外结构域的单跨膜蛋白。我们表征了对kv4.2介导的电流和DPPX亚家族蛋白的三个剪接变体的大鼠脑分布的调节作用。这三个剪接异构体- DPPX-S， DPPX-L；和DPPX-K -在成年大鼠脑中表达，并改变非洲爪蟾卵母细胞中表达的Kv4.2通道的电压依赖性和动力学特性。对缺乏可变n端的缺失突变体的分析表明，n端对Kv4通道的调制不是必需的。通过原位杂交分析，我们发现这三种剪接变体在Kv4亚基也表达的大脑区域显著表达。DPPX-K和DPPX-S mrna分布广泛，而DPPX-L转录本集中在大鼠大脑的少数特定区域。DPPX剪接变体的新出现的多样性，仅在蛋白质的n端不同，为Kv4通道的调节开辟了有趣的可能性。(c) 2006 Elsevier B.V.版权所有
Transient subthreshold-activating somato-dendritic A-type K+ currents (I(SA)s) have fundamental roles in neuronal function. They cause delayed excitation, influence spike repolarization, modulate the frequency of repetitive firing, and have important roles in signal processing in dendrites. We previously reported that DPPX proteins are key components of the channels mediating these currents (Kv4 channels) (Nadal, M.S., Ozaita, A., Amarillo, Y., Vega-Saenz, E., Ma, Y., Mo, W., Goldberg, E.M., Misumi, Y., Ikehara, Y., Neubert, T.A., Rudy, B., 2003. The CD26-related dipeptidyl aminopeptidase-like protein DPPX is a critical component of neuronal A-type K+ channels. Neuron 37, 449-461). The DPPX gene encodes alternatively spliced transcripts that generate single-spanning transmembrane proteins with a short, divergent intracellular domain and a large extracellular domain. We characterized the modulatory effects on Kv4.2-mediated currents and the rat brain distribution of three splice variants of the DPPX subfamily of proteins. These three splice isoforms - DPPX-S, DPPX-L; and DPPX-K - are expressed in adult rat brain and modify the voltage dependence and kinetic properties of Kv4.2 channels expressed in Xenopus oocytes. Analysis of a deletion mutant that lacks the variable N-terminus showed that the N-terminus is not necessary for the modulation of Kv4 channels. Using in situ hybridization analysis, we found that the three splice variants are prominently expressed in brain regions where Kv4 subunits are also expressed. DPPX-K and DPPX-S mRNAs have a widespread distribution, whereas DPPX-L transcripts are concentrated in few specific areas of the rat brain. The emerging diversity of DPPX splice variants, differing only in the N-terminus of the protein, opens up intriguing possibilities for the modulation of Kv4 channels. (c) 2006 Elsevier B.V. All rights reserved.