Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo
Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo
复制标题
DOI：
10.1074/jbc.272.42.26652
复制
发表时间：
1997-10-17
影响因子：
4.8
通讯作者：
Sugimoto, N
中科院分区：
文献类型：
--
作者：
Katahira, J;Sugiyama, H;Sugimoto, N
显示与来自Vero细胞的产气荚膜梭菌肠毒素（CPE）受体基因（CPE-R）同源的人和小鼠cDNA（DDBJ/EMBL/GenBank（TM）登录号D88492）（Katahira，J.，Inoue，N.，Horiguchi，Y.，Matsuda，M.，和Sugimoto，N.（1997）J. Cell Biol.136，1239-1247）。基于一级氨基酸序列的相似性，将它们分为两组，Vero细胞CPE受体同源物和大鼠雄激素戒断凋亡蛋白（RVP 1;登录号M74067）同源物。最初对CPE不敏感的L929细胞在用编码CPE受体或RVP 1同源物的cDNA转染后变得对CPE敏感，这表明这些基因产物不仅在结构上相似，而且作为CPE的受体在功能上是活性的。通过结合实验，人RVP 1同源物显示出与人CPE受体的亲和力和结合能力的差异，北方印迹分析显示CPE受体和RVP 1的小鼠同源物在小鼠小肠中大量表达。CPE受体mRNA在小肠中的表达仅限于隐蔽的肠上皮细胞，表明CPE受体在肠上皮细胞中表达。这些结果与CPE通过两种不同类型的受体与小肠细胞结合的报道一致。在其他器官中也检测到CPE-R和/或RVP 1 mRNA的高水平表达，包括肺、肝和肾，但在心脏和骨骼肌中仅低水平表达。这些结果表明，CPE在体内使用结构相关的细胞蛋白作为功能受体，迄今尚未被认为是CPE敏感的器官有可能成为CPE的靶点。
Human and mouse cDNAs showing homology to the Clostridium perfringens enterotoxin (CPE) receptor gene (CPE-R) from Vero cells (DDBJ/EMBL/GenBank(TM) accession no. D88492) (Katahira, J,, Inoue, N., Horiguchi, Y., Matsuda, M., and Sugimoto, N. (1997) J. Cell Biol. 136, 1239-1247) were cloned, They were classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal apoptosis protein (RVP1; accession no. M74067) homologues, based on the similarities of primary amino acid sequences. L929 cells that were originally insensitive to CPE became sensitive to CPE on their transfection with cDNAs encoding either the CPE receptor or RVP1 homologues, indicating that these gene products are not only structurally similar but also functionally active as receptors for CPE. Ey binding assay, the human RVP1 homologue showed differences in affinity and capacity of binding from those of the human CPE receptor, Northern blot analysis showed that mouse homologues of the CPE receptor and RVP1 are expressed abundantly in mouse small intestine. The expression of CPE-R mRNA in the small intestine was restricted to cryptic enterocytes, indicating that the CPE receptor is expressed in intestinal epithelial cells. These results are consistent with reports that CPE binds to the small intestinal cells via two different kinds of receptors, High levels of expression of CPE-R and/or RVP1 mRNA were also detected in other organs, including the lungs, liver, and kidneys, but only low levels were expressed in heart; and skeletal muscles. These results indicate that CPE uses structurally related cellular proteins as functional receptors in vivo and that organs that have not so far been recognized as CPE-sensitive have the potential to be targets of CPE.