Evolution of Cadherins and Associated Catenins

Abstract

During more than 600 Ma of multicellular animal evolution, the cadherin superfamily has become strikingly diverse, both structurally and functionally. Cadherins are typically transmembrane proteins with an ectodomain comprising so-called cadherin repeats. Cadherins are involved in cell–cell recognition, intercellular adhesion, and associated signaling, and are major players in morphogenesis and tissue behavior. Members of the three major cadherin families (cadherins, protocadherins, and cadherin-related proteins) differ in many aspects from each other. E-cadherin is the best-studied family member. Its cytoplasmic domain binds armadillo catenins, which form linkages to the cytoskeleton and trigger complex signaling pathways. Alpha-catenins play complementary roles. Even basal animals such as placozoans and cnidarians express several distinct cadherins and catenins, and their study may identify paradigms for ancient though crucial biological processes. The complex domain compositions of the different superfamily members and their respective functionalities appear to be key features of the emergence of multicellular animal life. Moreover, the origin of vertebrates coincided with a large increase in the number of cadherins and armadillo proteins, including modern molecules such as contemporary “classical” cadherins, clustered protocadherins and plakophilins. Although much needs to be learned about the biology of cadherins, the steadily increasing knowledge on cadherins is fascinating and points to key roles in many biological processes and in several important pathologies. This chapter focuses on the evolutionary relationships between different cadherin family members. The aim is to contribute to a deeper insight into their versatile roles in metazoans, and to foster further research on this remarkable superfamily.