Two novel CNRs from the CNR gene cluster have molecular features distinct from those of CNR1 to 8

Cadherin-related neuronal receptor (CNR) family proteins are known as synaptic cadherins and Reelin receptors. Here we have identified two novel mouse CNR genes, CNRcl and CNRc2, orthologues of human protocadherin (Pcdh) α-c1 and Pcdha-c2, respectively. While the variable large exons of CNRcl and c2 contain six conserved extracellular cadherin repeats (EC1-6) and are linked to the constant exons, both contain several molecular features distinct from CNR1-8. CNRcl and c2 lack the Arg-Gly-Asp (RGD) sequence that is conserved in the EC1 of CNR1-8, which is necessary for binding to Reelin. The present studies confirm that CNRcl and c2 failed to immunoprecipitate with Reelin. In addition, the regulation of novel CNR expression patterns during brain development is slightly different from that of CNR1. The identification of these new CNR genes characterized by their distinct extracellular function and expression is indicative of the novel diversity of the processes of brain structuring and synapse regulation.