Clustered protocadherins

Abstract

Nearly 60 cadherin superfamily adhesion molecules are encoded by the Pcdha, Pcdhb, and Pcdhg gene clusters. These so-called clustered protocadherins (Pcdhs) are broadly expressed throughout the nervous system, with lower levels found in a few nonneuronal tissues. Each neuron expresses a limited repertoire of clustered Pcdh genes, in a complicated process controlled by differential methylation and promoter choice. The clustered Pcdh proteins interact homophilically in trans as cis-multimers, which has the potential to generate a combinatorially explosive number of distinct adhesive interfaces that may give neurons unique molecular identities important for circuit formation. Functional studies of animals in which clustered Pcdhs have been deleted or disrupted demonstrate that these proteins play critical roles in neuronal survival, axon and dendrite arborization, and synaptogenesis. Additionally, they have been implicated in the progression of several cancers, suggesting that basic studies of their function and signaling pathways will have important future clinical applications. This chapter reviews the extant literature on this fascinating and important group of cell adhesion molecules, the most diverse within the larger cadherin superfamily.