CRC 492 B17 - Coupling integrin activation to the actin cytoskeleton

Basic data for this project

Description

Integrin-mediated cell adhesion between the extracellular matrix (ECM) and the actin cytoskeleton is crucial during the development of a multicellular organism. The linkage between integrins and the actin cytoskeleton involves a large variety of integrin-associated proteins regulating both assembly and disassembly of matrix adhesion complexes (MACs). Purified MACs also contain actin-nucleating factors such as Arp2/3 and formins and exhibit actin polymerization activity, suggesting that adhesion complexes actively participate in the linkage of ECM and the cytoskeleton. During the last funding period, we addressed the question of whether two main Arp2/3 activators, WASP and WAVE, are involved in the formation of matrix adhesion complexes in vivo during Drosophila development. Since WAVE activity is controlled by a conserved protein complex comprising Sra-1, Kette and Abi (SKA-complex), we also examined their roles in integrin-mediated cell adhesion during Drosophila development. In the course of our studies we realized that we had to establish novel molecular and genetic tools to thoroughly analyze the different integrin-dependent processes. Using these tools, we characterized cell-matrix interactions in both the developing wing and migrating glial cells of third instar larvae. Based on mutant analyses we found that Arp2/3 mediated actin nucleation is involved in the regulation of adhesion complex dynamics rather than in its formation. The temporally and spatially coordinated turnover of MACs is in particular important when cells change contact, as in dividing tissues or migrating cells, and will be the focus of the current application. In an independent series of experiments we determined the role of a large number of genes associated with linkage of integrins and the actin cytoskeleton for matrix dependent functions of glia cells. One of these genes is a collagen and will be studied in further detail.