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Published on: May 8, 2012
Efficient uptake of Yersinia pseudotuberculosis via integrin receptors involves a Rac1-Arp 2/3 pathway that bypasses
M A Alrutz1, A Srivastava, K W Wong
1Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue M and V 409, Boston, MA 02111, USA.
Molecular Microbiology
|November 28, 2001
Summary
Bacterial uptake into mammalian cells relies on invasin binding to integrins, requiring Rac1 and Arp 2/3. This pathway signals from the phagosome, independent of N-WASP.
Area of Science:
- Cell biology
- Microbiology
- Immunology
Background:
- Efficient bacterial internalization into host cells is crucial for pathogen survival and infection.
- Yersinia pseudotuberculosis utilizes invasin to bind beta1 integrins on mammalian cells, triggering uptake.
- The molecular mechanisms governing this specific host-pathogen interaction are not fully elucidated.
Purpose of the Study:
- To investigate the role of small GTPase Rac1 and the Arp 2/3 complex in Yersinia pseudotuberculosis uptake.
- To determine the signaling pathway from beta1 integrin engagement to Arp 2/3 activation during bacterial internalization.
- To ascertain whether N-WASP is essential for Rac1-mediated Arp 2/3 activation in this process.
Main Methods:
- Utilized mammalian cell culture and Yersinia pseudotuberculosis infection models.
- Employed Rac1-N17 dominant-negative mutant transfections to assess Rac1 function.
- Investigated Arp 2/3 complex involvement using Scar1/WAVE1 overproduction and WASP/N-WASP knockout cell lines.
- Monitored Rac1 activation and protein localization via biochemical assays and immunofluorescence microscopy.
Main Results:
- Bacterial uptake was dependent on functional Rac1 and Arp 2/3, with Rac1 activation observed upon integrin engagement.
- Rac1 and Arp 2/3 localized to nascent phagosomes, indicating a role in bacterial internalization.
- Overproduction of Scar1/WAVE1 sequestered Arp 2/3, significantly inhibiting bacterial uptake.
- Bacterial internalization proceeded normally in cells lacking WASP and N-WASP, suggesting an alternative signaling route.
Conclusions:
- Beta1 integrin-mediated Yersinia pseudotuberculosis uptake requires Rac1 and Arp 2/3 complex function.
- Rac1 signaling to Arp 2/3 occurs at the phagosome and can bypass N-WASP.
- These findings reveal a novel pathway for bacterial internalization mediated by host cell machinery.
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