Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia.
Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia.
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DOI：
10.1083/jcb.141.4.917
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发表时间：
1998-05-18
期刊：
影响因子：
--
通讯作者：
Lencer WI
中科院分区：
文献类型：
--
作者：
Wolf AA;Jobling MG;Wimer-Mackin S;Ferguson-Maltzman M;Madara JL;Holmes RK;Lencer WI
在极化细胞中，霍乱毒素(CT)的信号转导需要顶端内吞作用和逆行运输到高尔基池，可能还需要进入内质网(Lencer，WI.，C.Consted，S.Moe，M.Joering，H.M.Webb，S.Ruston，J.L.Madara，T.Hirst和R.Holmes)。1995年。J.细胞生物学。131：951-962)。在这项研究中，我们测试了CT的顶膜受体神经节苷脂GM1是否在毒素作用中起特异性作用。为了做到这一点，我们使用了CT和相关的大肠杆菌热不稳定的II型肠毒素LTIIb。CT和LTIIb通过不同的受体结合B亚基在细胞表面区分神经节苷脂GM1和GD1a。然而，具有酶活性的A亚基是同源的。虽然两种毒素都能与人肠道T84细胞(Kd≈5 nM)特异性结合，但只有CT能引起cAMP依赖的CL-−分泌反应。然而，LTIIb在诱导小鼠Y1肾上腺细胞的cAMP依赖反应方面比CT更有效(毒性剂量为10pg/孔，而不是300pg/孔)。在T84细胞中，CT有小凹样洗涤剂不溶于膜，而LTIIb没有。为了进一步研究神经节苷脂结合的专一性和分配到不溶于洗涤剂的膜与信号转导之间的关系，制备了CT和LTIIb嵌合毒素。对这些嵌合毒素的分析证实，毒素诱导的信号转导关键依赖于神经节苷脂结构的特异性。神经节苷脂GM1在信号转导中的作用机制(S)可能依赖于CT与小窝或小窝相关膜域的偶联。
In polarized cells, signal transduction by cholera toxin (CT) requires apical endocytosis and retrograde transport into Golgi cisternae and perhaps ER (Lencer, W.I., C. Constable, S. Moe, M. Jobling, H.M. Webb, S. Ruston, J.L. Madara, T. Hirst, and R. Holmes. 1995. J. Cell Biol. 131:951–962). In this study, we tested whether CT's apical membrane receptor ganglioside GM1 acts specifically in toxin action. To do so, we used CT and the related Escherichia coli heat-labile type II enterotoxin LTIIb. CT and LTIIb distinguish between gangliosides GM1 and GD1a at the cell surface by virtue of their dissimilar receptor-binding B subunits. The enzymatically active A subunits, however, are homologous. While both toxins bound specifically to human intestinal T84 cells (K d ≈ 5 nM), only CT elicited a cAMP-dependent Cl− secretory response. LTIIb, however, was more potent than CT in eliciting a cAMP-dependent response from mouse Y1 adrenal cells (toxic dose 10 vs. 300 pg/well). In T84 cells, CT fractionated with caveolae-like detergent-insoluble membranes, but LTIIb did not. To investigate further the relationship between the specificity of ganglioside binding and partitioning into detergent-insoluble membranes and signal transduction, CT and LTIIb chimeric toxins were prepared. Analysis of these chimeric toxins confirmed that toxin-induced signal transduction depended critically on the specificity of ganglioside structure. The mechanism(s) by which ganglioside GM1 functions in signal transduction likely depends on coupling CT with caveolae or caveolae-related membrane domains.
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影响因子：
4.8
作者：
HANADA, K;NISHIJIMA, M;PAGANO, RE
通讯作者：
PAGANO, RE
影响因子：
4.8
作者：
Lencer, WI;Constable, C;Hirst, TR
通讯作者：
Hirst, TR
DOI：
10.1083/jcb.129.3.619
发表时间：
1995-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gorodinsky A;Harris DA
通讯作者：
Harris DA
DOI：
10.1083/jcb.118.5.1003
发表时间：
1992-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kurzchalia TV;Dupree P;Parton RG;Kellner R;Virta H;Lehnert M;Simons K
通讯作者：
Simons K
影响因子：
3.1
作者：
FUKUTA, S;MAGNANI, JL;GINSBURG, V
通讯作者：
GINSBURG, V