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

VL - 115

SP - 2669

EP - 2678

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - Pt 13

ER -