Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations
Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations
复制标题
DOI：
10.1152/ajpcell.00090.2006
复制
发表时间：
2006-10-01
影响因子：
5.5
通讯作者：
Moriyama, Yoshinori
中科院分区：
文献类型：
--
作者：
Hiasa, Miki;Matsumoto, Takuya;Moriyama, Yoshinori
MATE 1是第一个被鉴定的多药和毒素排出（MATE）蛋白家族的哺乳动物实例。人MATE 1（hMATE 1）主要表达并定位于肾小管和胆小管的管腔膜，并介导毒性有机阳离子（OC）的H+偶联电中性排泄进入尿液和胆汁（Otsuka M，松本T，Morimoto R，Arioka S，Omote H，and Moriyama Y. Proc Natl Acad Sci USA 102：17923-17928，2005）。mMATE 1是一种小鼠MATE直系同源物，也主要在肾脏和肝脏中表达，尽管其转运特性尚未得到表征。在本研究中，我们研究了mMATE 1的传输特性和定位。在HEK-293细胞中表达该蛋白后，mMATE 1介导电中性H+/四乙基铵交换，并显示出与hMATE 1相似的底物特异性。使用针对mMATE 1的特异性抗体结合RT-PCR的免疫学技术显示，mMATE 1也在各种细胞中表达，包括脑胶质样细胞和毛细血管、胰管细胞、膀胱上皮、肾上腺皮质、胰岛α细胞、Leydig细胞和维生素A储存Ito细胞。这些结果表明mMATE 1是一种多特异性H+/OC交换剂。mMATE 1出乎意料的广泛分布表明，该转运蛋白参与了除从体内排泄OC以外的多种生物学功能。
MATE1 was the first mammalian example of the multidrug and toxin extrusion (MATE) protein family to be identified. Human MATE1 (hMATE1) is predominantly expressed and localized to the luminal membranes of the urinary tubules and bile canaliculi and mediates H+-coupled electroneutral excretion of toxic organic cations (OCs) into urine and bile (Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, and Moriyama Y. Proc Natl Acad Sci USA 102: 17923-17928, 2005). mMATE1, a mouse MATE ortholog, is also predominantly expressed in kidney and liver, although its transport properties are not yet characterized. In the present study, we investigated the transport properties and localization of mMATE1. Upon expression of this protein in HEK-293 cells, mMATE1 mediated electroneutral H+/ tetraethylammonium exchange and showed a substrate specificity similar to that of hMATE1. Immunological techniques with specific antibodies against mMATE1 combined with RT-PCR revealed that mMATE1 is also expressed in various cells, including brain glia-like cells and capillaries, pancreatic duct cells, urinary bladder epithelium, adrenal gland cortex, alpha cells of the islets of Langerhans, Leydig cells, and vitamin A-storing Ito cells. These results indicate that mMATE1 is a polyspecific H+/OC exchanger. The unexpectedly wide distribution of mMATE1 suggests involvement of this transporter protein in diverse biological functions other than excretion of OCs from the body.