Molecular evolution of the junctophilin gene family
Molecular evolution of the junctophilin gene family
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DOI：
10.1152/physiolgenomics.00017.2009
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发表时间：
2009-05-01
影响因子：
4.6
通讯作者：
Wehrens, Xander H. T.
中科院分区：
文献类型：
--
作者：
Garbino, Alejandro;van Oort, Ralph J.;Wehrens, Xander H. T.
Garbino A，货车Oort RJ，Diplomat SS，Landstrom AP，阿克曼MJ，Wehrens XHT.嗜连接蛋白基因家族的分子进化。Physiol Genomics 37：175-186，2009.首次发表于2009年3月24日; doi：10.1152/physiolgenomics.00017.2009.-嗜连接蛋白（JPH）是连接膜复合物蛋白家族的成员，对于质膜和肌质/内质网膜的物理接近是重要的。因此，JPH促进可兴奋细胞中质膜电压门控钙通道和细胞内钙释放通道之间的信号转导。为了确定JPH基因家族的分子进化，我们对来自40多个物种的60多个JPH基因进行了系统发育分析，并比较了不同物种和不同亚型之间的保守性。我们发现，JPH是进化高度保守的，特别是在所有物种中发现的膜占据和识别连接基序。我们的数据表明，JPH的祖先形式出现在一个共同的后生动物祖先的最新和脊椎动物的四个亚型出现，可能是两轮的全基因组复制。通过将多重预测技术与序列比对相结合，我们还假设存在新的重要功能区域和翻译后修饰的候选位点。越来越多的可用序列产生显着的洞察JPH的分子进化。我们的分析是一致的新兴的概念，JPHs在可兴奋细胞中具有双重重要功能：连接膜复合物的结构组装和细胞内钙信号通路的调节。
Garbino A, van Oort RJ, Dixit SS, Landstrom AP, Ackerman MJ, Wehrens XHT. Molecular evolution of the junctophilin gene family. Physiol Genomics 37: 175-186, 2009. First published March 24, 2009; doi:10.1152/physiolgenomics.00017.2009.-Junctophilins (JPHs) are members of a junctional membrane complex protein family important for the physical approximation of plasmalemmal and sarcoplasmic/endoplasmic reticulum membranes. As such, JPHs facilitate signal transduction in excitable cells between plasmalemmal voltage-gated calcium channels and intracellular calcium release channels. To determine the molecular evolution of the JPH gene family, we performed a phylogenetic analysis of over 60 JPH genes from over 40 species and compared conservation across species and different isoforms. We found that JPHs are evolutionary highly conserved, in particular the membrane occupation and recognition nexus motifs found in all species. Our data suggest that an ancestral form of JPH arose at the latest in a common metazoan ancestor and that in vertebrates four isoforms arose, probably following two rounds of whole genome duplications. By combining multiple prediction techniques with sequence alignments, we also postulate the presence of new important functional regions and candidate sites for posttranslational modifications. The increasing number of available sequences yields significant insight into the molecular evolution of JPHs. Our analysis is consistent with the emerging concept that JPHs serve dual important functions in excitable cells: structural assembly of junctional membrane complexes and regulation of intracellular calcium signaling pathways.