New insights into FAK structure and function in focal adhesions

10 p.-4 fig.Focal adhesion kinase (FAK; also known as PTK2) was discovered three decades ago and is now recognised as a key player in the regulation of cell–matrix adhesion and mesenchymal cell migration. Although it is essential during development, FAK also drives invasive cancer progression and metastasis. On a structural level, the basic building blocks of FAK have been described for some time. However, a picture of how FAK integrates into larger assemblies in various cellular environments, including one of its main cellular locations, the focal adhesion (FA) complex, is only beginning to emerge. Nano-resolution data from cellular studies, as well as atomic structures from reconstituted systems, have provided first insights, but also point to challenges that remain for obtaining a full structural understanding of how FAK is integrated in the FA complex and the structural changes occurring at different stages of FA maturation. In this Review, we discuss the known structural features of FAK, the interactions with its partners within the FA environment on the cell membrane and propose how its initial assembly in nascent FAs might change during FA maturation under force.D.L. is funded by the Ministerio de Ciencia, Innovación y Universidades for the Spanish State Research Agency Retos (grant RTI2018-099318-B-I00), and from the Ministerio de Ciencia e Innovación for the Generation of Knowledge (grant PID2021-127058NB-I00), both co-funded by the European Regional Development Fund (FEDER).Peer reviewe