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Involvement of the Golgi region in the intracellular trafficking of cholera toxin
Author(s) -
Nambiar Madhusoodana P.,
Oda Tatsuya,
Chen Chaohua,
Kuwazuru Yasuo,
Wu Henry C.
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041540203
Subject(s) - brefeldin a , cholera toxin , intracellular , golgi apparatus , forskolin , biology , microbiology and biotechnology , secretion , internalization , cytotoxicity , toxin , endocytosis , endosome , cell , biochemistry , receptor , endoplasmic reticulum , in vitro
The intracellular pathway following receptor‐mediated endocytosis of cholera toxin was studied using brefeldin A (BFA), which inhibited protein secretion and induced dramatic morphological changes in the Golgi region. In both mouse Y1 adrenal cells and CHO cells, BFA at 1 μg/ml caused a 80–90% inhibition of the cholera toxin (CT)‐elevation of intracellular cAMP. The inhibition of the cytotoxicity of CT by BFA was also observed in a rounding assay of Y1 adrenal cells. The inhibition of CT cytotoxicity by BFA was dose dependent, with the ID 50 value similar to the LD 50 of BFA in Y1 adrenal cells. Binding and internalization of [ 125 I]‐cholera toxin in Y1 adrenal cells was not affected by BFA. Unlike the BFA‐sensitive cell lines such as Y1 adrenal and CHO cells, BFA at 1 μg/ml did not inhibit the cytotoxicity of CT in PtK 1 cells, of which the Golgi structure was BFA‐resistant. These results strongly suggest that a BFA‐sensitive Golgi is required for the protection of CT cytotoxicity by BFA. In contrast, elevation of the intracellular cAMP by forskolin, which acts directly on the plasma membrane adenylate cyclase, was not affected by BFA. These observations indicate that the intoxication of target cells by CT requires an intact Golgi region for its intracellular trafficking and/or processing. In this respect, CT shares a common intracellular pathway with ricin, Pseudomonas toxin, and modeccin, even though their structures and modes of action are very different. © 1993 Wiley‐Liss, Inc.