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

The molecular machinery involved in clathrin mediated endocytosis (CME) forms two distinct structures at the plasma membrane: clathrin coated pits and flat clathrin lattices. Clathrin coated pits are the canonical endocytic carriers for CME and have been extensively studied. In contrast, the cellular role of flat clathrin lattices, characterised by their stability, are not well understood. Here we show that flat clathrin lattices mediate the formation of a special type of cellular adhesions, called reticular adhesions, in a process controlled by the composition of the extracellular matrix. We observed that cells plated on fibronectin displayed few flat clathrin lattices and reticular adhesions. Notably, this effect occurred locally in cells, in an extracellular matrix-contact dependent manner. Inhibition of the CME machinery led to complete disappearance of reticular adhesions and live-cell imaging showed that flat clathrin lattice assembly is required for the establishment of reticular adhesions. Manipulation of the fibronectin receptor integrin β1 revealed that the formation of flat clathrin lattices - and consequently reticular adhesions - are controlled by the activity of this receptor. CME and other endocytic routes have conventionally been linked to the disassembly of cellular adhesions by mediating the internalisation of their components. Our results present a novel paradigm in the relationship between these two processes by showing that endocytic proteins can also play a role in the assembly of cellular adhesions. ### Competing Interest Statement The authors have declared no competing interest.