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

我们先前从兔脑脉络丛中克隆了一个新的蛋白质，命名为parclin。该蛋白已被我们鉴定为一种磷酸化蛋白，可在刺激胃酸分泌的过程中从壁细胞胞浆转位至分泌膜。后来的研究发现，parclin在与水运动有关的各种组织中都有特异性表达，如脉络丛。由于Parclin的C末端与CLIC家族蛋白的序列相同，被认为是细胞内的氯离子通道，因此推测该分子通过控制氯离子电导来调节水的运动。随后，我们培育出了Parclin基因敲除小鼠，这是CLIC家族的第一只小鼠。与我们的预期相反，这只老鼠没有表现出任何明显的表型。尤其是小鼠，虽然酸性分泌细胞表现出最高的副花青素表达，但其酸性分泌能力正常。这可能是由于生长过程中补偿蛋白(S)的表达，也可能是由于一种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了转录组分析。在胃粘膜中，一些与胃酸分泌相关的基因差异表达，在脉络丛中，许多基因与各种离子通道有关。此外，还提示未知剪接变异体(S)至少在脉络丛中有表达。在另一项单独的研究中，Syntenin被确定为Parclin相互作用蛋白。Syntenin有两个PDZ结构域，建议参与细胞内的交通。

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.