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

我们以前从兔脑脉络丛中克隆了一个新蛋白，命名为parchorin。该蛋白被我们鉴定为一种磷酸化蛋白，它在刺激壁细胞泌酸的过程中从胞浆转移到分泌膜上。随后的工作揭示parchorin在参与水运动的各种组织中特异性表达，如脉络丛。由于parchorin的C-末端与CLIC家族蛋白（被认为是细胞内氯离子通道）中发现的C-末端具有共同序列，因此表明该分子通过控制氯离子电导来调节水运动。本研究建立了Parchorin基因敲除小鼠，这是CLIC家族的第一个敲除小鼠。与我们的预期相反，小鼠没有显示任何明显的表型。特别是，小鼠表现出正常的泌酸能力，虽然泌酸细胞表现出最高的parchorin表达。这可能是由于在生长过程中补偿蛋白的表达，或者是由于完全出乎意料的可能的生理功能。然后，我们使用基因芯片对野生型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差异表达，在脉络丛中，许多与各种离子通道相关的基因差异表达。此外，有人建议，未知的剪接变异体至少可以在脉络丛中表达。在另一项研究中，syntenin被鉴定为parchorin相互作用蛋白。Syntenin具有两个PDZ结构域，并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.