Sara A. Wickström: "Mechanisms of cellular force generation in matrix remodeling and fibrosis"

Sara A. Wickström
MPI for Biology of Ageing, Cologne, Germany

Mechanisms of cellular force generation in matrix remodeling and fibrosis

In order to establish and maintain structural organization and proper function of the tissue, cells need to sense and process extracellular signals. These signals comprise of soluble factors as well as structural determinants such as the extracellular matrix (ECM). The ECM not only provides positional cues and a structural platform for cell attachment, but also propagates signals that regulate cell fate and behavior. Interactions between cells and the ECM are regulated by integrins, which are α/β heterodimeric cell surface proteins and the main receptors for ECM components. Since integrins have short cytoplasmic tails that lack enzymatic activity, they recruit a large number of scaffold and signaling proteins to their cytoplasmic tails upon ligand binding. FAs not only activate a range of signaling pathways but also provide a link between the integrins and the actin cytoskeleton. This linkage enables cells to generate force on the ECM and thereby to execute a number of essential integrin functions, including cell shape changes, regulation of cell polarity, migration, and ECM remodeling. Integrin-linked kinase (ILK) has been shown to play an essential role in the establishment and maintenance of the integrin-actin connection, but the exact function of this protein has long remained unclear and controversial due to its various reported catalytic and scaffolding properties. I will discuss the recent advances in understanding the properties and functions of ILK.