International Research Center for Infectious Diseases

Laboratory of Infection Cell Biology

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Research Group

SA ProfessorYukako Fujinaga
SA Assistant ProfessorYo Sugawara
SA Assistant ProfessorTakuhiro Matsumura

Research Projects

Research Projects: Many bacterial toxins are able to damage the host severely, even at very low concentrations. Most bacterial toxins are enzymes that act catalytically and with high specificity on the functional host cell molecules, thereby markedly modulating host homeostasis. The toxins are also often highly efficient in accessing their target molecule in the host. The ingenious transport systems involved often exploit the fundamental machinery of membrane trafficking and the functions of intracellular organelles. Studies that elucidate toxin trafficking could provide valuable information about basic cellular function, aid our understanding of the pathology induced by these toxins, and help in the development of effective therapeutic strategies against them. Our laboratory group is studying the transport mechanisms of the botulinum neurotoxin complex, which must pass through the digestive tract and cross the epithelial barrier lining the intestine to cause food-borne botulism.


Hypothetical model for intestinal absorption of botuliunum neurotoxin complex (type B 16S toxin). We propose a three-step mechanism by which the botulinum neurotoxin complex breaches the intestinal epithelial barrier. (1) Apically located 16S toxin is transcytosed.(2) Once located in the basolateral compartment, HA of the 16S toxin binds to E-cadherin, and thereby disrupts the paracellular barrier. (3) A large amount of toxin accumulates in the basolateral area via paracellular movement.

Major publications

  1. Sugawara Y, Fujinaga Y. The botulinum toxin complex meets E-cadherin on the way to its destination. Cell Adh Migr. 2011; 5(1): 34-36. [総説]
  2. Sugawara Y, Matsumura T, Takegahara Y, Jin Y, Tsukasaki Y, Takeichi M, Fujinaga Y. Botulinum HA disrupts the intercellular epithelial barrier by directly binding E-cadherin. J Cell Biol. 2010; 189 (4), 691-700
  3. Jin Y1, Takegahara Y1, Sugawara Y, Matsumura T, Fujinaga Y. Disruption of the epithelial barrier by botulinum hemagglutinin (HA) proteins - Differences in cell tropism and the mechanism of action between HA proteins of types A or B, and HA proteins of type C. Microbiology. 2009; 155(Pt 1): 35-45. 1 These authors are contributed equally.
  4. Matsumura T, Jin Y, Kabumoto Y, Takegahara Y, Oguma K, Lencer WI, Fujinaga Y. The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption. Cell Microbiol. 2008; 10(2): 355-364.
  5. Matsumura T1, Fujinaga Y1, Jin Y, Kabumoto Y, Oguma K. Human milk SIgA binds to botulinum type B 16S toxin and limits toxin adherence on T84 cells. Biochem Biophys Res Commun. 2007; 352(4), 867-872.


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