Your browser doesn't support javascript.

Biblioteca Virtual em Saúde

Brasil

Home > Pesquisa > ()
Imprimir Exportar

Formato de exportação:

Exportar

Email
Adicionar mais destinatários
| |

Frizzled proteins are colonic epithelial receptors for C. difficile toxin B.

Tao, Liang; Zhang, Jie; Meraner, Paul; Tovaglieri, Alessio; Wu, Xiaoqian; Gerhard, Ralf; Zhang, Xinjun; Stallcup, William B; Miao, Ji; He, Xi; Hurdle, Julian G; Breault, David T; Brass, Abraham L; Dong, Min.
Nature; 538(7625): 350-355, 2016 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-27680706
Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium. Colonic organoids cultured from FZD7-knockout mice, combined with knockdown of FZD1 and 2, showed increased resistance to TcdB. The colonic epithelium in FZD7-knockout mice was less susceptible to TcdB-induced tissue damage in vivo. These findings establish FZDs as physiologically relevant receptors for TcdB in the colonic epithelium.
Selo DaSilva