Cadherins: Fundamental Social Interaction

Social interactions between cells are absolutely necessary. Possibly the most fundamental social interaction is those that hold cells together. Cohesion between cells is essential to form organized multicellular structures, that can respond and withstand various external forces that mean to pull them apart. Cell cohesion is governed by a complex network of proteins and polysaccharide chains. These mechanisms of cohesion govern the architecture of the body and the making and breaking of these attachments control the orientation and behavior of the cell’s cytoskeleton. One of these proteins of cohesion is Cadherins. Cadherins are cytoskeleton-linked transmembrane proteins that mostly mediate attachment of a cell to another. Their primary function
The cytoplasmic domain of these classical cadherins is highly conserved and binds directly to several cytoplasmic proteins, two such proteins are beta-catenin and p120. Classical cadherins primarily form homophilic cell-cell interactions, tend to be concentrated in the adheren junctions, and modulate adhesion through dynamic interaction with the actin cytoskeleton. Homophilic binding occurs at the N-terminus, the domains that lie farthest from the membrane. These terminal domains form a knob and a nearby pocket, the cadherin molecules protruding from the opposite cell membrane bind by insertion of the knob of one domain into the pocket of the other. Classical cadherins, in particular, interact indirectly, and link with actin in the cytosolic domain with the help of adapter proteins mentioned previously beta-catenin, p120, and alpha-catenin. Classical cadherins participate in key morphogenetic roles in diverse tissues throughout development, specifically in the morula stage. Cell sorting, coordinated cell movements, planar cell division, and formation and maintenance of boundaries in tissues. They do this by allowing cells of similar type to stick together and stay separated from other types of cells, they are not like glue but rather mediate highly selective
One interesting thing about protocadherins is that homologs have not been found in Drosophilia or Caenorhabditis elegans. They are transmembrane proteins like classical cadherins, except their extracellular domain has six to seven repeats that lack the conserved sequence elements present in classical cadherins. Protocadherins are classified into three gene clusters: Pcdh-α; Pcdh-β; and Pcdh-γ, each with unique gene structures that encode constant and variable domains. All three clusters of Pcdh have been found throughout the neuronal soma, dendrites, and axons. They have a remarkably similar genomic structure resembling that of immunoglobins. Their abundance in the nervous system along with their diversity and unique gene structure has led to the speculation that protocadherins are involved in the wiring of neural circuits. Each neural circuit possesses a fingerprint of protocadherins, that not only distinguishes it from other circuits is required to initiate connections with other circuits during nervous system development (Halbleib J, and Nelson, W. 2006). In addition to cell-cell adhesion via hemophilic interactions, protocadherins mediate intracellular signaling, all three classes of Pcdh have distinct cytoplasmic regions, which do not contain recognizable motifs and lack the catenin-binding domains found in classical