TRANSCYTOSIS OF CHOLERA-TOXIN SUBUNITS ACROSS MODEL HUMAN INTESTINAL EPITHELIA
TRANSCYTOSIS OF CHOLERA-TOXIN SUBUNITS ACROSS MODEL HUMAN INTESTINAL EPITHELIA
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DOI：
10.1073/pnas.92.22.10094
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发表时间：
1995-10-24
影响因子：
11.1
通讯作者：
MADARA, JL
中科院分区：
文献类型：
--
作者：
LENCER, WI;MOE, S;MADARA, JL
霍乱毒素(CT)通过结合顶端受体(神经节苷脂G(M1))，最终激活基底外侧效应器(腺苷环化酶)，引起肠上皮细胞的大量分泌反应。然而，从根尖到基底外侧膜的信号转导机制尚不清楚。我们之前已经证明，CT对极化的人类肠道上皮细胞系T84的作用需要内吞作用，并在多个细胞内隔间进行处理。我们在本研究中的目的是验证这样的假设，即CT实际上可能通过囊泡运输移动到其作用于基底外侧膜的部位。与心尖受体结合后，CT进入基底侧定向的跨细胞囊泡。CTB亚基和CTA亚基都完整地传递到基底膜的浆膜表面，毒素不通过细胞间连接扩散穿过单层。CT B亚单位的跨胞作用表现出与CT诱导的Cl-分泌几乎相同的时间进程和温度依赖性--表明两者可能有关。这些数据确定了一种机制，可以解释毒素的尖端受体和基底外侧效应器之间的联系。
Cholera toxin (CT) elicits a massive secretory response from intestinal epithelia by binding apical receptors (ganglioside G(M1)) and ultimately activating basolateral effecters (adenylate cyclase). The mechanism of signal transduction from apical to basolateral membrane, however, remains undefined. We have previously shown that CT action on the polarized human intestinal epithelial cell line T84 requires endocytosis and processing in multiple intracellular compartments. Our aim in the present study was to test the hypothesis that CT may actually move to its site of action on the basolateral membrane by vesicular traffic. After binding apical receptors, CT entered basolaterally directed transcytotic vesicles. Both CT B subunits and to a lesser extent CT A subunits were delivered intact to the serosal surface of the basolateral membrane, The toxin did not traverse the monolayer by diffusion through intercellular junctions. Transcytosis of CT B subunits displayed nearly identical time course and temperature dependency with that of CT-induced Cl- secretion-suggesting the two may be related. These data identify a mechanism that may explain the link between the toxin's apical receptor and basolateral effector.