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

点击翻译按钮获取中文摘要

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.