The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption.
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.
Matsumura
Takuhiro
T
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.
Jin
Yingji
Y
Kabumoto
Yuko
Y
Takegahara
Yuki
Y
Oguma
Keiji
K
Lencer
Wayne I
WI
Fujinaga
Yukako
Y
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
D006388:Hemagglutinins; D046911:Macromolecular Substances; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A