Postsynaptic and differential localization to neuronal subtypes of protocadherin β16 in the mammalian central nervous system

The formation of synapses is dependent on the expression of surface adhesion molecules that facilitate correct recognition, stabilization and function. The more than 60 clustered protocadherins (Pcdh alpha, Pcdh beta and Pcdh gamma) identified in human and mouse have attracted considerable attention because of their clustered genomic organization and the potential role of alpha- and gamma-Pcdhs in allocating a neuronal surface code specifying synaptic connectivity. Here, we investigated whether beta-Pcdhs also contribute to these processes. By performing RT-PCR, we found a striking parallel onset of expression of many beta-Pcdhs around the onset of neurogenesis and wide expression in the central nervous system. We generated antibodies specific to Pcdhb16 and showed localization of Pcdhb16 protein in the adult mouse cerebellum, hippocampus and cerebral cortex. Analysing the mouse retina in detail revealed localization of Pcdhb16 to specific cell types and, importantly, subsets of synapses. We show that Pcdhb16 localizes predominantly to postsynaptic compartments and the comparison with Pcdhb22 implies differential localization and functions of individual beta-Pcdhs in the mammalian central nervous system. Moreover, we provide evidence for a role of beta-Pcdhs in the outer segments and connecting cilia of photoreceptors. Our data show for the first time that beta-Pcdhs also localize to specific neuronal subpopulations and synapses, providing support for the hypothesis that clustered Pcdhs are candidate genes for the specification of synaptic connectivity and neuronal networks.