Speaker Professor David Calderwood, Professor of Pharmacology and Cell Biology, Yale School of Medicine

Tilte Imaging Integrin and extracellular matrix traffic

 Host Maddy Parsons

 

Abstract The ability of animal cells to sense, adhere to and remodel their local extracellular matrix (ECM) is central to control of cell shape, mechanical responsiveness, motility and signaling, and hence to development, tissue formation, wound healing and the immune response. Cell-ECM interactions occur predominantly via clustered transmembrane receptors of the integrin family at various specialized, multi-protein adhesion complexes (including focal adhesions) that physically link the ECM to the cytoskeleton and the intracellular signaling apparatus. Using functional recombinant β1 integrins with traceable tags inserted in an extracellular loop and the key ECM protein fibronectin tagged with a pH-sensitive fluorophore we have observed integrin and ECM trafficking in live cells. We reveal targeted delivery of integrin-containing vesicles to focal adhesions and find that fibronectin is secreted predominantly in bursts under stabilized lamellipodia at the leading edge of polarized cells. Locally secreted fibronectin then undergoes β1 integrin-dependent fibrillogenesis.