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Bromberger T, Klapproth S, Rohwedder I, et al. Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking. Front Immunol. 2021;12:702345doi: 10.3389/fimmu.2021.702345.
Bromberger, T., Klapproth, S., Rohwedder, I., Weber, J., Pick, R., Mittmann, L., Min-Weißenhorn, S. J., Reichel, C. A., Scheiermann, C., Sperandio, M., & Moser, M. (2021). Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking. Frontiers in immunology, 12702345. https://doi.org/10.3389/fimmu.2021.702345
Bromberger, Thomas, et al. "Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking." Frontiers in immunology vol. 12 (2021): 702345. doi: https://doi.org/10.3389/fimmu.2021.702345
Bromberger T, Klapproth S, Rohwedder I, Weber J, Pick R, Mittmann L, Min-Weißenhorn SJ, Reichel CA, Scheiermann C, Sperandio M, Moser M. Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking. Front Immunol. 2021 Aug 19;12:702345. doi: 10.3389/fimmu.2021.702345. eCollection 2021. PMID: 34489950; PMCID: PMC8417109.
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Front Immunol. 2021 Aug 19;12:702345. doi: 10.3389/fimmu.2021.702345. eCollection 2021.

Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking.

Frontiers in immunology

Thomas Bromberger, Sarah Klapproth, Ina Rohwedder, Jasmin Weber, Robert Pick, Laura Mittmann, Soo Jin Min-Weißenhorn, Christoph A Reichel, Christoph Scheiermann, Markus Sperandio, Markus Moser

Affiliations

  1. Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, Technische Universität München, Munich, Germany.
  2. Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
  3. Walter Brendel Center of Experimental Medicine (WBex), Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Martinsried, Germany.
  4. Department of Pathology and Immunology, School of Medicine, University of Geneva, Geneva, Switzerland.
  5. Walter Brendel Centre of Experimental Medicine (WBex), Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
  6. Department of Otorhinolaryngology, Ludwig-Maximilians-Universität München, Munich, Germany.
  7. Transgenic Core Facility, Max Planck Institute of Biochemistry, Martinsried, Germany.

PMID: 34489950 PMCID: PMC8417109 DOI: 10.3389/fimmu.2021.702345

Abstract

β2 integrins mediate key processes during leukocyte trafficking. Upon leukocyte activation, the structurally bent β2 integrins change their conformation towards an extended, intermediate and eventually high affinity conformation, which mediate slow leukocyte rolling and firm arrest, respectively. Translocation of talin1 to integrin adhesion sites by interactions with the small GTPase Rap1 and the Rap1 effector Riam precede these processes. Using Rap1 binding mutant talin1 and Riam deficient mice we show a strong Riam-dependent T cell homing process to lymph nodes in adoptive transfer experiments and by intravital microscopy. Moreover, neutrophils from compound mutant mice exhibit strongly increased rolling velocities to inflamed cremaster muscle venules compared to single mutants. Using Hoxb8 cell derived neutrophils generated from the mutant mouse strains, we show that both pathways regulate leukocyte rolling and adhesion synergistically by inducing conformational changes of the β2 integrin ectodomain. Importantly, a simultaneous loss of both pathways results in a rolling phenotype similar to talin1 deficient neutrophils suggesting that β2 integrin regulation primarily occurs

Copyright © 2021 Bromberger, Klapproth, Rohwedder, Weber, Pick, Mittmann, Min-Weißenhorn, Reichel, Scheiermann, Sperandio and Moser.

Keywords: Rap1; Riam; integrin activation; leukocyte adhesion; leukocyte rolling; leukocyte trafficking; talin

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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