Cloning and functional characterization of a novel up-regulator, cartregulin, of carnitine transporter, OCTN2
Cloning and functional characterization of a novel up-regulator, cartregulin, of carnitine transporter, OCTN2
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DOI：
10.1016/j.abb.2006.06.006
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发表时间：
2006-08-01
影响因子：
3.9
通讯作者：
Miwa, Soichi
中科院分区：
文献类型：
--
作者：
Nagai, Kazuhiko;Takikawa, Osamu;Miwa, Soichi
乙酰肉碱对包括阿尔茨海默病在内的一些神经系统疾病有治疗作用。OCTN2是已知的乙酰肉碱的转运体，但它在大脑中的表达非常低。为了检测乙酰肉碱的脑特异性转运蛋白，我们使用OCTN家族中保守的DNA探针，通过杂交筛选了一个大鼠脑cDNA文库。获得了一个与OCTN2c DNA同源的基因。该基因编码一个新的146个氨基酸的蛋白，具有一个可能的跨膜结构域。该基因不仅在大鼠脑组织中表达，在其他组织中也有表达。该新蛋白在COS-7细胞中表达时定位于内质网，但对乙酰肉碱没有转运活性。然而，当与OCTN 2共表达时，它使OCTN 2介导的转运增加了约两倍。伴随着增强的是信使核糖核酸和蛋白质水平的增加。在非洲爪哇卵母细胞中注射OCTN2基因后，通过共表达这种新蛋白，OCTN2的转运活性增强。这些数据表明，该新蛋白通过稳定内质网中的mRNA而增加OCTN_2。该蛋白可能是OCTN2的上调蛋白，暂时被命名为CartRegin。(C)2006 Elsevier Inc.保留所有权利。
Acetylcarnitine exerts therapeutic effects on some neurological disorders including Alzheimer's disease. OCTN2 is known as a transporter for acetylcarnitine, but its expression in the brain is very low. To examine a brain-specific transporter for acetylcarnitine, we screened a rat brain cDNA library by hybridization using a DNA probe conserved among an OCTN family. A cDNA homologous to OCTN2 cDNA was isolated. The cDNA encoded a novel 146-amino acid protein with one putative transmembrane domain. The mRNA was expressed not only in rat brain but also in some other tissues. The novel protein was localized in endoplasmic reticulum when expressed in COS-7 cells but exhibited no transport activity for acetylcarnitine. However, when co-expressed with OCTN2, it enhanced the OCTN2-mediated transport by about twofold. The enhancement was accompanied by an increase in the levels of mRNA and protein. When OCTN2 was expressed in Xenopus oocytes by injection of its cRNA, its transport activity was enhanced by co-expression of the novel protein. These data suggest that the novel protein increases OCTN2 by stabilizing the mRNA in endoplasmic reticulum. The protein may be an up-regulator of OCTN2 and is tentatively designated cartregulin. (c) 2006 Elsevier Inc. All rights reserved.