New tools to study the interaction between integrins and latent TGFβ1.

ABSTRACT: Transforming growth factor beta (TGFβ) 1 regulates cell differentiation and proliferation in different physiological settings, but is also involved in fibrotic progression and protects tumors from the immune system. Integrin αVβ6 has been shown to activate latent TGFβ1 by applying mechanical forces onto the latency-associated peptide (LAP). While the extracellular binding between αVβ6 and LAP1 is well characterized, less is known about the cytoplasmic adaptations that enable αVβ6 to apply such forces. Here, we generated new tools to facilitate the analysis of this interaction. We combined the integrin-binding part of LAP1 with a GFP and the Fc chain of human IgG. This chimeric protein, sLAP1, revealed a mechanical rearrangement of immobilized sLAP1 by αVβ6 integrin. This unique interaction was not observed between sLAP1 and other integrins. We also analyzed αVβ6 integrin binding to LAP2 and LAP3 by creating respective sLAPs. Compared to sLAP1, integrin αVβ6 showed less binding to sLAP3 and no rearrangement. These observations indicate differences in the binding of αVβ6 to LAP1 and LAP3 that have not been appreciated so far. Finally, αVβ6-sLAP1 interaction was maintained even at strongly reduced cellular contractility, highlighting the special mechanical connection between αVβ6 integrin and latent TGFβ1.

SUBMITTER: Bachmann M 

PROVIDER: S-EPMC9901185 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature