Pathophysiological Analysis of Parchorin, Specifically Expressed in Water-Transporting Tissues

此前我们从兔脑脉络膜丛中克隆了一种新的蛋白，命名为parchorin。该蛋白被鉴定为一种从细胞质转移到家兔壁细胞分泌膜的磷酸化蛋白，与刺激胃酸分泌有关。随后的研究表明，parchorin在参与水运动的各种组织（如脉络膜丛）中特异性表达。parchorin的c端与CLIC家族蛋白的c端序列相同，被认为是细胞内的氯离子通道，提示该分子通过控制氯离子电导来调节水的运动。随后，我们研制出了首个用于CLIC家族的parchorin敲除小鼠。与我们的预期相反，小鼠没有表现出任何明显的表型。特别是小鼠分泌酸的能力正常，尽管分泌酸的细胞中parchorin的表达量最高。这可能是由于生长过程中代偿蛋白的表达，也可能是由于完全意想不到的生理功能。然后，我们使用基因芯片对野生小鼠和基因敲除小鼠的胃粘膜和脉络丛进行转录组分析。在胃粘膜中，一些与胃酸分泌相关的基因被差异表达，在脉络丛中，许多与各种离子通道相关的基因被差异表达。此外，我们认为未知的剪接变异可能至少在脉络膜丛中表达。在另一项研究中，syntenin被确定为parchorin相互作用蛋白。Syntenin有两个PDZ结构域，被认为参与细胞内运输。

We previously cloned a new protein from rabbit brain choroid plexus and named as parchorin. This protein had been identified by us as a phosphoprotein which translocated from cytosol to secretory membrane of rabbit parietal cell in association with stimulation of acid secretion. Subsequent works revealed that parchorin was specifically expressed in various tissues involving in water movement, such as choroid plexus. As the C-terminal of parchorin has common sequence to that found in CLIC family proteins, which are considered to be intracellular chloride channel, it is suggested that this molecule is regulating water movement via the control of chloride conductance. We then produced parchorin knock-out mouse, which is the first one for CLIC family. Contrary to our expectation, the mouse did not show any apparent phenotypes. Especially, the mouse showed normal acid secretory capacity although acid-secreting cell shows the highest parchorin expression. This could be due either to the expression of compensatory protein(s) during the process of growth, or to a possible physiological function that is totally unexpected. We then performed transcriptome analysis of the gastric mucosa and choroid plexus of wild and knock-out mice using GeneChip. In the gastric mucosa, some genes related to gastric acid secretion were differentially expressed, and in the choroid plexus, many genes related to various ion channels. Furthermore, it was suggested that unknown splicing variant (s) could be expressed at least in the choroid plexus. In a separate study, syntenin was identified as parchorin-interacting protein. Syntenin has two PDZ domains and suggested to be involved in intracellular traffic.