The cadherin superfamily

The poster provides an overview of the cadherin superfamily, depicting representative molecules for several subfamilies, and displaying the plethora of molecular arrangements character-istic of these molecules (see Commentary by Angst, Marcozzi and Magee on p. 629). Classical cadherins form lateral dimers and typically mediate homophilic adhesion between neighbouring cells and linkage to the actin filament network via their cytoplasmic binding partners α-catenin,

β-catenin and vinculin. Desmosomal cadherins, and VE-cadherin, interact with armadillo family members plakoglobin and/or plakophilins, as well as desmoplakins, to link to the intermediate filament system. Desmosomal cadherin lateral and head-to-head interactions may be homophilic or heterophilic. The adhesive and lateral interactions of other cadherins are less well understood. Very large cadherins, such as FAT family members, may not be involved in adhesion at all, but rather may have a repulsive or sensing role.

Some cadherins may activate signalling pathways via SRC-family kinases (e.g. CNR-cadherins via FYN, and raft-associated T-cadherin) and/or G-proteins (e.g. 7TM cadherins and T-cadherin), although these interactions are currently poorly understood. Other cadherins (e.g. μ-protocadherin) may mediate the assembly of multiprotein complexes through scaffolding domains (e.g. PDZ and proline-rich domains).

Examples of the genomic organisation of cadherins are shown on the left. Although isolated cadherin genes can be found within the genome, cadherin genes frequently occur in groups, the organisations of which are strikingly different. Many classical cadherin genes are linked on human chromosome 16q22 (upper panel in the figure). Desmosomal cadherin genes (middle panel) are clustered on human chromosome 18q12; the correlation of their gene order and direction of transcription (indicated by arrows) points to the existence of long-range genetic elements within this gene cluster. Three protocadherin clusters (PCDHα, PCDHβ and PCDH γ) are localised on human chromosome 5q31 and share very similar genome organisation; the PCDHα (CNR cadherin) cluster is given as an example (lower panel). The extracellular (EC) region of each of the clustered protocadherins is encoded by a single uninterrupted exon that is differentially spliced to the cytoplasmic constant region, which is encoded by three exons. Two examples (EC region 1 and EC region 13) are shown.

Electronic copies of the full-size poster insert are available in the online version of this article (see www.biologists.com/jcs). Files in several formats are provided and may be downloaded for use as slides.