Research Department "Molecular Medicine" (Reinhard Fässler)
Integrins are cell surface receptors that bind proteins of the extracellular matrix and associate with the actin cytoskeleton. The ligand binding property of integrins requires a pre-activation step that is characterized by a conformational change of the ectodomain and separation of the transmembrane and cytoplasmic domains. Following ligand binding integrins cluster and assemble gigantic signaling hubs that contain hundreds of proteins. With the help of these signaling hubs and the connection to the acto-myosin network integrins are able to trigger biochemical signals and to transduce and receive mechanical signals. The residence time of integrins on the cell surface is short and within a few minutes they internalize and most of them recycle back to the cell surface. This intracellular trafficking profoundly affects integrin function, signaling properties and cell surface distribution. Furthermore, there is accumulating evidence that integrins are checked for their integrity in endosomes and if damaged, they are sorted for lysosomal degradation. In our laboratory we study how integrins become activated, how they execute their signaling tasks, why they recycle, and how a damaged integrin is recognized in endsomomes.