Focal adhesion dynamics in cellular function and disease

Abstract

Acting as a bridge between the cytoskeleton of the cell and the extra cellular matrix (ECM), the cell-ECM adhesions with integrins at their core, play a major role in cell signalling to direct mechanotransduction, cell migration, cell cycle progression, proliferation, differentiation, growth and repair. Biochemically, these adhesions are composed of diverse, yet an organised group of structural proteins, receptors, adaptors, various enzymes including protein kinases, phosphatases, GTPases, proteases, etc. as well as scaffolding molecules. The major integrin adhesion complexes (IACs) characterised are focal adhesions (FAs), invadosomes (podosomes and invadopodia), hemidesmosomes (HDs) and reticular adhesions (RAs). The varied composition and regulation of the IACs and their signalling, apart from being an integral part of normal cell survival, has been shown to be of paramount importance in various developmental and pathological processes. This review per-illustrates the recent advancements in the research of IACs, their crucial roles in normal as well as diseased states. We have also touched on few of the various methods that have been developed over the years to visualise IACs, measure the forces they exert and study their signalling and molecular composition. Having such pertinent roles in the context of various pathologies, these IACs need to be understood and studied to develop therapeutical targets. We have given an update to the studies done in recent years and described various techniques which have been applied to study these structures, thereby, providing context in furthering research with respect to IAC targeted therapeutics.