Flat Clathrin Lattices Nucleate Reticular Adhesions in an Integrin β1 Activity-Dependent Manner

Reticular adhesions (RAs) consist of integrin αvβ5 and harbor flat clathrin lattices (FCLs), long-lasting structures with similar molecular composition as clathrin mediated endocytosis (CME) carriers. Why FCLs and RAs colocalize is not known. Here, we show that FCLs assemble RAs in a process controlled by fibronectin (FN) and its receptor, integrin α5 β1. We observed that cells on FN-rich matrices displayed fewer FCLs and RAs. CME machinery inhibition abolished RAs and live-cell imaging showed that RA establishment requires FCL co-assembly. The inhibitory activity of FN was mediated by the activation of integrin α5 β1 at Tensin1-positive fibrillar adhesions. Conventionally, endocytosis disassembles cellular adhesions by internalizing their components. Our results present a novel paradigm in the relationship between these two processes by showing that endocytic proteins can actively function in the assembly of cell adhesions. Furthermore, we show this novel adhesion assembly mechanism is coupled to cell migration via unique crosstalk between cell matrix adhesions.