Thinnes F P, Reymann S
Max-Planck Institute for Experimental Medicine, Göttingen, Germany.
Naturwissenschaften. 1997 Nov;84(11):480-98. doi: 10.1007/s001140050432.
Eukaryotic porin can be considered to be a good candidate for forming the channel component of the protein complex which, depending on the approach used, may realize its expression either as the outwardly-rectifying depolarization-induced chloride channel or as the volume-sensitive organic osmolyte-anion channel. As a basis for this proposition, we point to a series of correspondences in properties between mammalian porin and the ORDIC channel complex. Specifically, mammalian porin is expressed in the plasmalemma of different cells and chloride channels can be blocked by anti-human porin antibodies in astrocytes and endothelial cells. There is an indication of colocalisation of human porin and the cystic fibrosis (CF) gene product, CFTR, in the apical region of epithelial cells. The primary structure of porin from a CF patient was found to be normal. Cytosol and amniotic fluid fractions influence the channel characteristics of mammalian porin. Channel-active mammalian porin binds ATP and the stilbene disulphonate grouping of the chloride channel inhibitor DIDS. Human porin in black membranes is a pathway for taurine, and biogenic polyamines reduce the voltage dependence of human porin. Assuming the relationship between human porin and the ORDIC channel/VSOAC complex, studies on plasmalemma-integrated human porin have a relevance for CF research. In addition, we refer to a case study on a child with encephalomyopathy in which porin could not be detected using monoclonal anti-human porin antibodies. Our studies were based on purified and sequenced human porin from different cells and from different cell compartments. In addition, we raised antibodies against mature human porin or synthetic parts of the molecule. This provided a firm foundation for our topochemical work with which we were able to establish the multi-topological expression of eukaryotic porin channels. The data are summarized and discussed.
真核孔蛋白可被视为形成蛋白质复合体通道成分的良好候选者，根据所采用的方法，该复合体可能表现为外向整流的去极化诱导氯离子通道或容积敏感性有机渗透质阴离子通道。作为这一观点的依据，我们指出哺乳动物孔蛋白与ORDIC通道复合体在性质上存在一系列对应关系。具体而言，哺乳动物孔蛋白在不同细胞的质膜中表达，并且星形胶质细胞和内皮细胞中的氯离子通道可被抗人孔蛋白抗体阻断。有迹象表明人孔蛋白与囊性纤维化（CF）基因产物CFTR在上皮细胞顶端区域共定位。发现一名CF患者的孔蛋白一级结构正常。胞质溶胶和羊水组分影响哺乳动物孔蛋白的通道特性。具有通道活性的哺乳动物孔蛋白结合ATP以及氯离子通道抑制剂DIDS的二苯乙烯二磺酸盐基团。黑膜中的人孔蛋白是牛磺酸的一条通道，生物源性多胺降低人孔蛋白的电压依赖性。假设人孔蛋白与ORDIC通道/VSOAC复合体之间存在关联，对整合在质膜中的人孔蛋白的研究与CF研究相关。此外，我们提及一项关于一名患有脑肌病儿童的病例研究，在该研究中使用单克隆抗人孔蛋白抗体未能检测到孔蛋白。我们的研究基于从不同细胞和不同细胞区室纯化并测序的人孔蛋白。此外，我们制备了针对成熟人孔蛋白或该分子合成片段的抗体。这为我们的拓扑化学研究提供了坚实基础，通过该研究我们能够确定真核孔蛋白通道的多拓扑表达。对数据进行了总结和讨论。
