title: The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption.
abstract: The type B botulinum neurotoxin (BoNT) elicits flaccid paralysis and death in humans by intoxicating peripheral nerves after oral absorption. Here, we examine the function of the haemagglutinin (HA), a non-toxic component of the large 16S BoNT complex. We find that the HA acts in the intestine to disrupt epithelial barrier function by opening intercellular tight and adherens junctions. This allows transport of BoNT and other large solutes into the systemic circulation and explains how the type B BoNT complexes are efficiently absorbed. In vitro, HA appears to act on the epithelial cell via the basolateral membrane only, suggesting the possibility of another step in the absorptive process. These studies show that the 16S BoNT complex is a multifunctional protein assembly equipped with the machinery to efficiently breach the intestinal barrier and act systemically on peripheral nerves.
authors.affiliation: Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Matsumura
authors.forename: Yingji
authors.initials: Y
authors.lastname: Jin
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kabumoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takegahara
authors.forename: Keiji
authors.initials: K
authors.lastname: Oguma
authors.forename: Wayne I
authors.initials: WI
authors.lastname: Lencer
authors.forename: Yukako
authors.initials: Y
authors.lastname: Fujinaga
mesh_terms: D000818:Animals; D001692:Biological Transport; D001905:Botulinum Toxins / Q000493:pharmacokinetics*; D019274:Botulinum Toxins, Type A; D018938:Caco-2 Cells; D004285:Dogs; D017097:Electric Impedance; D006388:Hemagglutinins / Q000494:pharmacology*; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects* / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology; D007700:Kinetics; D046911:Macromolecular Substances / Q000493:pharmacokinetics
chemical_list: D006388:Hemagglutinins; D046911:Macromolecular Substances; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A