Fine-tuning integrin adhesion, trafficking and signalling through post-translational modification

Integrins are heterodimeric adhesion receptors that orchestrate cell-extracellular matrix (ECM) interactions to transduce mechanical and biochemical signals and regulate cell behaviour. Their activity, trafficking and signalling are finely tuned by post-translational modifications (PTMs), which include glycosylation, phosphorylation, disulfide bond formation, ubiquitylation and acetylation. Although numerous PTMs have been experimentally validated on specific integrin α- and β-subunits, large-scale proteomic and PTM screening studies have revealed additional putative regulatory sites whose functional significance remains unexplored. This Review surveys high-throughput PTM datasets for integrin isoforms, highlighting both established modifications with demonstrated roles in folding, ligand binding or adhesion complex assembly, alongside candidate PTMs that might represent underappreciated layers of integrin regulation. By looking at putative PTMs beside validated sites, this Review provides a basis for prioritising future functional studies, with the goal of better understanding how combinatorial modifications encode the dynamic behaviours of integrins in homeostasis, development and disease, particularly cancer and metastasis.