Transport of the botulinum neurotoxin–associating protein, nontoxic nonhemagglutinin, across the rat small intestinal epithelial cell monolayer


Correspondence: Toshihiro Watanabe, Department of Food and Cosmetic Science, Faculty of Bioindustry, Tokyo University of Agriculture, 196 Yasaka, Abashiri 099-2493, Japan. Tel.: +81 152 48 3843; fax: +81 152 48 2940; e-mail:


Botulinum neurotoxin (BoNT) associates with nontoxic nonhemagglutinin (NTNHA) yielding a complex in culture. BoNT and NTNHA have similar domain organizations, implying that they share common functions, although this remains unclear. Here, we examined cell monolayer transport of serotype D NTNHA in the rat intestinal epithelial cell line IEC-6. NTNHA and BoNT both bound to the cell and were transported across the cell layer. NTNHA contains a QXW motif and a β-trefoil fold, both common in sugar chain–recognizing proteins, whereas the QXW motif is absent in all BoNT serotypes. This could explain the distinct sugar chain–recognizing properties of NTNHA and BoNT.