The cadherin-related neuronal receptor family: a novel diversified cadherin family at the synapse.

The cadherin-related neuronal receptor (CNR) family has been identified as a receptor family that cooperates with Fyn, a member of the Src family of tyrosine kinases. The CNR family is composed of 14 members in mice and 15 members in humans. The mRNAs of CNRs are highly expressed in the brain and CNR1 protein is localized at synaptic junctions. Hence CNR family proteins are synaptic cadherins. The unique structure of CNR family cDNAs, which is characterized by complete DNA sequence identity among their 3'-termini including a part of the coding region, prompted us to investigate the genomic organization of this family. The genomic organization of CNRs is divided into 'variable' and 'constant' region exons, analogous to immunoglobulin and T cell receptor gene clusters. This organization raised the possibility that the CNR gene cluster may undergo somatic DNA rearrangement or trans-splicing and produce diversified gene products. Although it is not yet clear that the CNR gene cluster in the neuronal genomic DNA is somatically changed, a recent study suggested the occurrence of trans-transcripts and accumulation of somatic mutations in CNR transcripts (Genes Cells 6 (2001) 151). These results suggested that the proteins from the CNR gene cluster are enormously diversified by unique mechanisms. The localization of CNR1 protein at the synapse and the diversity of CNRs led us to the hypothesis that gene regulation of the CNR family dictates the formation and reorganization of synaptic connections in the nervous system.