Alpha Yap: Cadherins hold it all together

H omotypic adhesion between surface receptors called cadherins is essential to the integrity of epithelial sheets. But cadherins aren't just passive anchors that allow cells to stick together. Instead, by coupling to the actin cytoskeleton, they can generate tension to affect the structure and resiliency of individual cells and tissues. How are contractile forces generated at cadherin junctions, and how are forces transmitted across junctions to neighboring cells in the epithelial sheet? Having studied cell–cell adhesions since the start of his research career (1, 2), Alpha Yap has a good appreciation for the complexity of cytoskel-etal regulation at cell–cell junctions (3–5) and is now poised to answer these questions. We called him at his lab at Australia's University of Queensland to hear how he's weaving his past experience into new insights on junction structure and function. Did you always want to be a scientist? Well, fi rst I wanted to be a tennis player, but I was too short, had no talent, and had bad vision. Later I wanted to be a professional musician and sing in a choir, but again I lacked talent. My son and daughter somehow have this talent, and my daughter is actually a professional musician, but I think my singing then and subsequently may qualify as cruel and unusual punishment for anyone who hears it. [Laughs] Then in high school, I had an idealized vision of—this sounds terribly pretentious—a scholarly life. So I suppose, deep down, that's what I wanted. But after high school I went into medicine instead, because in Australia at that time one could go straight to medical school after high school. I took a medical degree and trained in a hospital for several years as a specialist physician and endocrinologist. But then I decided to go to the lab and do a PhD. I still do a little bit of clinical endocrinology, but it's a tiny part of what I do now. Why did you switch to research? You know, I don't think I ever made a considered decision to pursue a research career instead of medicine. At some point I just realized that, although there's a profound human satisfaction in helping people and it can be enormously satisfying to reach a diagnosis for a patient, the intellectual satisfaction derived from that is very short-lived. By contrast, a happy research life is sort of a slow burn. In fact, research is …