Open AccessThe HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption
Author(s) -
Matsumura Takuhiro,
Jin Yingji,
Kabumoto Yuko,
Takegahara Yuki,
Oguma Keiji,
Lencer Wayne I.,
Fujinaga Yukako
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.01048.x
Subject(s) - adherens junction , biology , tight junction , microbiology and biotechnology , intracellular , toxin , cell junction , barrier function , botulism , neurotoxin , biophysics , cell , biochemistry , cadherin
Summary 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.