The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cells.
Orally ingested botulinum toxin enters the circulatory system and eventually reaches the peripheral nerves, where it elicits a response of neurological dysfunction. In this study, we report the important findings concerning the mechanism of Clostridium botulinum type C progenitor toxin (C16S) endocytic mechanism. C16S toxin bound to high molecular weight proteins on the surface of human colon carcinoma HT-29 cells and was internalized, but not if the cells were pretreated with neuraminidase. Benzyl-GalNAc which inhibited O-glycosylation of glycoproteins also interfered in the toxin's ability to bind the cell surface. On the other hand, the toxin was internalized in spite of pretreatment of the cells with PPMP, an inhibitor of ganglioside synthesis. These results suggest that the glycoproteins, like mucin, fulfill the important roles of receptor and transporter of C16S toxin.
Nishikawa
Atsushi
A
Department of Applied Biological Science, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan. nishikaw@cc.tuat.ac.jp
Uotsu
Nobuo
N
Arimitsu
Hideyuki
H
Lee
Jae-Chul
JC
Miura
Yutaka
Y
Fujinaga
Yukako
Y
Nakada
Hiroshi
H
Watanabe
Toshihiro
T
Ohyama
Tohru
T
Sakano
Yoshiyuki
Y
Oguma
Keiji
K
D001905:Botulinum Toxins / Q000378:metabolism*; D006031:Glycosylation; D019073:HT29 Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D009439:Neuraminidase / Q000494:pharmacology; D011485:Protein Binding; D021381:Protein Transport
D009439:Neuraminidase; D001905:Botulinum Toxins; C096324:botulinum toxin type C