Reticular adhesions are assembled at flat clathrin lattices and opposed by active integrin α5β1

Abstract

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 RAs are assembled at FCLs in a process controlled by fibronectin (FN) and its receptor, integrin α5β1. 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 coassembly. The inhibitory activity of FN was mediated by the activation of integrin α5β1 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.

Flat clathrin lattices are linked to metastatic potential in colorectal cancer

“…For instance, there is growing evidence of an intimate relationship between FCLs and integrin αVβ5-containing reticular adhesions. 14 , 41 , 42 , 43 Alternatively, mechanobiological cues could play a role in FCL formation, since an altered plasma membrane tension 12 and certain properties of the extracellular environment like rigidity and presentation of adhesion ligands 12 , 38 , 43 , 44 , 45 , 46 were reported to affect the presence of alternative CCSs.…”

Flattening out: A new ESCRT structure in cell adhesions

“…Recent studies have identified other integrin adhesions that are also actin independent, namely reticular adhesions ( 9 ). These contain specific integrins, flat AP2-rich clathrin lattices, and are connected to specific ECM proteins ( 10 ). Whereas the molecular composition of canonical, actin-associated focal adhesion is well-studied ( 11 ), the molecular composition and ultrastructure of reticular adhesions and novel ESCRT-III-positive integrin adhesions remain largely a mystery.…”