What is "protocadherin"

n. (context biology English) Any of several polypeptides that are fragments of cadherin

Protocadherins (Pcdhs) are the largest mammalian subgroup of the cadherin superfamily of homophilic cell-adhesion proteins. They were discovered by Shintaro Suzuki's group, when they used PCR to find new members of the cadherin family. The PCR fragments that corresponded to Protocadherins were found in vertebrate and invertebrate species This prevalence in a wide range of species suggested that the fragments were part of an ancient cadherin and were thus termed "Protocadherins" as the "first cadherins"; although, of the approximately 70 Pcdh genes identified in mammalian genomes, over 50 are located in tightly linked gene clusters on the same chromosome, and this kind of organization can only be found in vertebrates.

In mammals, two types of Pcdh genes have been defined: the non-clustered Pcdhs which are scattered throughout the genome; and the clustered Pcdhs organized in three gene clusters designated α, β, γ which in mouse genome comprises 14, 22 and 22, respectively, large variable exons arrayed in tandem(Fig.1). Each exon is transcribed from its owner promoter and encodes: the entire extracellular domain, a transmembrane domain, and a short and variable intracellular domain of the corresponding Pcdh protein which differs from the Cadherin intracellular domain due to lack of attachment to the cytoskeleton through catenins(Fig.2).

Moreover, these clustered Pcdh genes are predominantly expressed in the developing nervous system and since different subsets of Pcdhs genes are differentially expressed in individual neurons, a vast cell surface diversity may arise from this combinatorial expression. This has led to speculation and further to the proposal that Pcdhs may provide a synaptic-address code for neuronal connectivity or a single-cell barcode for self-recognition/self-avoidance similar to that ascribed to DSCAM proteins of invertebrates. Although vertebrate DSCAMs lack the diversity of their invertebrate counterparts, the selective transcription of individual Pcdh isoforms can be achieved by promoter choice followed by alternative pre-mRNA cis-splicing thus increasing the number of possible combinations.