Imtiaz, Sarah2019-01-112019-01-112017-11http://hdl.handle.net/2003/3787110.17877/DE290R-19858Cell adhesion and migration require a tightly regulated organization of cytoskeleton and cell-matrix adhesion sites which are large protein complexes consisted of multiple components. To address the question how the core focal adhesion (FA) proteins mediate the adhesion segregation process to form fibrillar adhesions (FB) and how they regulate cell motility, a high-content imaging screen was employed using combinatorial RNAi for 10 FA proteins. This revealed distinct FA proteins directly influence the segregation of adhesion sites, suggesting the modular assembly and function of adhesion sites. We identified three distinct modules: signaling, actin-regulatory and adhesion building-segregating module. Signaling proteins such as FAK and p130CAS as well as actin-regulatory proteins (VASP, α-actinin-1, zyxin) control the localization of tensin-1 in FA, which is the hallmark of FB. Structural proteins (kindlin-2, ILK and talin-1) modulate the translocation of tensin-1 from focal adhesion to FB. Notably the same set of proteins, were associated with specific modes of migration. Signaling and actin-regulatory module is linked to enhance cell migration (amoeboid and lamellipodial modes), whereas the adhesion building-segregating module is related to impaired migration (confined mode). Taken together, this study shows that FA are composed of different functional modules that distinctly control different stages of the adhesion transformation process and the cell migration behavior.enfocal adhesionsdistinct modulesadhesion segregationcell migration570doctoral thesisFokale AdhäsionZellmigration