Binding of Rap1 and Riam to Talin1 Fine-Tune beta 2 Integrin Activity During Leukocyte Trafficking

Bromberger, Thomas; Klapproth, Sarah; Rohwedder, Ina; Weber, Jasmin; Pick, Robert; Mittmann, Laura; Min-Weissenhorn, Soo Jin; Reichel, Christoph A.; Scheiermann, Christoph; Sperandio, Markus und Moser, Markus (19. August 2021): Binding of Rap1 and Riam to Talin1 Fine-Tune beta 2 Integrin Activity During Leukocyte Trafficking. In: Frontiers in Immunology, Bd. 12, 702345

Abstract

beta 2 integrins mediate key processes during leukocyte trafficking. Upon leukocyte activation, the structurally bent beta 2 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 beta 2 integrin ectodomain. Importantly, a simultaneous loss of both pathways results in a rolling phenotype similar to talin1 deficient neutrophils suggesting that beta 2 integrin regulation primarily occurs via these two pathways.

• Dokumententyp: Zeitschriftenartikel
• Keywords: talin; Riam; Rap1; leukocyte adhesion; leukocyte rolling; integrin activation; leukocyte trafficking
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1664-3224
• Sprache: Englisch