Tyrosine phosphorylation controls cortactin binding to two enterohaemorrhagic Escherichia coli effectors: Tir and EspFu/TccP.
Enterohaemorrhagic Escherichia coli (EHEC) is an important food-borne pathogen that, upon infection, causes destruction of the microvilli brush border of intestinal cells. EHEC is able to recruit several host cell proteins and induce actin accumulation beneath its adherence site, forming a pedestal-like structure upon which the bacterium is firmly attached. Injection of bacterial effectors into the host cells is required to trigger the recruitment and activation of proteins, such as cortactin, neural Wiskott-Aldrich syndrome protein (N-WASP) and Arp2/3 complex, directly involved in the actin polymerization process. We found that cortactin, an actin-binding protein, has a pivotal role during pedestal formation by EHEC. Cortactin was found to bind directly to two important virulence factors of EHEC, Tir and EspF(u), which are translocated into the host cells during infection. Binding of cortactin to these effectors is dependent upon tyrosine phosphorylation and a balance between tyrosine phosphorylation and dephosphorylation of cortactin is required to regulate pedestal formation by EHEC.
Cantarelli
Vlademir V
VV
Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. vcantarelli@weinmann.com.br
Kodama
Toshio
T
Nijstad
Niels
N
Abolghait
Said Kamal
SK
Nada
Shigeyuki
S
Okada
Masato
M
Iida
Tetsuya
T
Honda
Takeshi
T
D000199:Actins / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D051356:Cortactin / Q000378:metabolism*; D019453:Escherichia coli O157 / Q000378:metabolism / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000382:microbiology; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
D000199:Actins; D002352:Carrier Proteins; D051356:Cortactin; D029968:Escherichia coli Proteins; C489109:EspFU protein, E coli; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli; D037521:Virulence Factors; C505370:tccP protein, E coli; D014443:Tyrosine