Speaker
Description
The interplay between inside-out and outside-in activation of integrin receptor orchestrates cell motility and tissue regeneration. While such mechanisms of RGD-binding integrin, including integrin beta1 and beta3, are well documented, mechano-sensitive regulations of integrin beta6 remain largely unknown. Using the viscous RGD-membrane as the model system, we find that integrin beta6 and viscous RGD ligands promptly colocalize and assemble dense micrometer-sized clusters in the early phase of adhesion formation (15-min). However, these clusters gradually dissipate, and integrin beta6 and RGD ligands become poorly colocalized (60-min). With the tail-swapping and mutagenesis approach, we find that interactions between the cytoplasmic tail of integrin beta6 and kindlin, rather than talin, act as the critical factor to regulate the adhesion stability. In addition, we will report our latest findings in kindlin-dependent integrin beta6 adhesion assembly and cell migration on compliant surface. Our results suggest that kindlin-mediated inside-out activation can bypass the extracellular force dependent signalling and orchestrate the spatiotemporal assembly of integrin beta6.
