Drosophila vinculin is more harmful when hyperactive than absent, and can circumvent integrin to form adhesion complexes.

Vinculin is a highly conserved protein involved in cell adhesion and mechanotransduction, and both gain and loss of its activity causes defective cell behaviour. Here, we examine how altering vinculin activity perturbs integrin function within the context of Drosophila development. Whereas loss of vinculin produced relatively minor phenotypes, gain of vinculin activity, through a loss of head-tail autoinhibition, caused lethality. The minimal domain capable of inducing lethality is the talin-binding D1 domain, and this appears to require talin-binding activity, as lethality was suppressed by competition with single vinculin-binding sites from talin. Activated Drosophila vinculin triggered the formation of cytoplasmic adhesion complexes through the rod of talin, but independently of integrin. These complexes contain a subset of adhesion proteins but no longer link the membrane to actin. The negative effects of hyperactive vinculin were segregated into morphogenetic defects caused by its whole head domain and lethality caused by its D1 domain. These findings demonstrate the crucial importance of the tight control of the activity of vinculin.

The many faces of cell adhesion during Drosophila muscle development.

Muscle development involves a series of morphogenetic events including cell fusion, migration and epidermal attachment. At various points in this complex developmental program, regulation of muscle-muscle and muscle-epidermal adhesion is crucial. One of the best-characterised adhesion events is the formation of stable, integrin-based adhesions at the attachment sites formed between the ends of muscles and epidermal cells, but other adhesion mechanisms are involved in earlier stages. Here we review recent work from Drosophila on the role of adhesion during muscle development, situating integrin function within the wider developmental program.

Anchors and signals: the diverse roles of integrins in development.

Integrins mediate cell adhesion by providing a link between the actin cytoskeleton and the extracellular matrix. As well as acting to anchor cells, integrin adhesions provide sensory input via mechanotransduction and synergism with signaling pathways, and provide the cell with the conditions necessary for differentiation in a permissive manner. In this review, we explore how integrins contribute to development, and what this tells us about how they work. From a signaling perspective, the influence of integrins on cell viability and fate is muted in a developmental context as compared to cell culture. Integrin phenotypes tend to arise from a failure of normally specified cells to create tissues properly, due to defective adhesion. The diversity of integrin functions in development shows how cell adhesion is continuously adjusted, both within and between animals, to fit developmental purpose.