TY - JOUR
T1 - Role of the beta1-integrin cytoplasmic tail in mediating invasin-promoted internalization of Yersinia.
AU - Gustavsson, Anna
AU - Armulik, Annika
AU - Brakebusch, Cord
AU - Fässler, Reinhard
AU - Johansson, Staffan
AU - Fällman, Maria
N1 - Keywords: Adhesins, Bacterial; Amino Acid Motifs; Antigens, CD29; Cell Adhesion; Cell Communication; Cell Membrane; Enzyme Inhibitors; Mutation; Phagocytosis; Protein Binding; Protein Isoforms; Tyrosine; Vitronectin; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis Infections
PY - 2002
Y1 - 2002
N2 - Invasin of Yersinia pseudotuberculosis binds to beta1-integrins on host cells and triggers internalization of the bacterium. To elucidate the mechanism behind the beta1-integrin-mediated internalization of Yersinia, a beta1-integrin-deficient cell line, GD25, transfected with wild-type beta1A, beta1B or different mutants of the beta1A subunit was used. Both beta1A and beta1B bound to invasin-expressing bacteria, but only beta1A was able to mediate internalization of the bacteria. The cytoplasmic region of beta1A, differing from beta1B, contains two NPXY motifs surrounding a double threonine site. Exchanging the tyrosines of the two NPXYs to phenylalanines did not inhibit the uptake, whereas a marked reduction was seen when the first tyrosine (Y783) was exchanged to alanine. A similar reduction was seen when the two nearby threonines (TT788-9) were exchanged with alanines. It was also noted that cells affected in bacterial internalization exhibited reduced spreading capability when seeded onto invasin, suggesting a correlation between the internalization of invasin-expressing bacteria and invasin-induced spreading. Likewise, integrins defective in forming peripheral focal complex structures was unable to mediate uptake of invasin-expressing bacteria.
AB - Invasin of Yersinia pseudotuberculosis binds to beta1-integrins on host cells and triggers internalization of the bacterium. To elucidate the mechanism behind the beta1-integrin-mediated internalization of Yersinia, a beta1-integrin-deficient cell line, GD25, transfected with wild-type beta1A, beta1B or different mutants of the beta1A subunit was used. Both beta1A and beta1B bound to invasin-expressing bacteria, but only beta1A was able to mediate internalization of the bacteria. The cytoplasmic region of beta1A, differing from beta1B, contains two NPXY motifs surrounding a double threonine site. Exchanging the tyrosines of the two NPXYs to phenylalanines did not inhibit the uptake, whereas a marked reduction was seen when the first tyrosine (Y783) was exchanged to alanine. A similar reduction was seen when the two nearby threonines (TT788-9) were exchanged with alanines. It was also noted that cells affected in bacterial internalization exhibited reduced spreading capability when seeded onto invasin, suggesting a correlation between the internalization of invasin-expressing bacteria and invasin-induced spreading. Likewise, integrins defective in forming peripheral focal complex structures was unable to mediate uptake of invasin-expressing bacteria.
M3 - Journal article
C2 - 12077358
SN - 0021-9533
VL - 115
SP - 2669
EP - 2678
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - Pt 13
ER -