Alpha-protocadherins are presynaptic and axonal in nicotinic pathways

Abstract

The protocadherin families pcdh-α, β, and γ have been proposed to mediate synaptic specificity via homophilic interactions. Here we report isolation of two pcdh-α family members from chick. We find pcdh-α mRNA in multiple regions of chick CNS including cerebellum, tectum, olfactory bulb, and forebrain, and in the autonomic nervous system. Immunoblots identify major components of 120 and 140 kDa both in brain and ciliary ganglion extracts. Immunohistochemistry reveals pcdh-αs in axons and perisynaptically in preganglionic terminals, adjacent to transmitter release sites. Pcdh-αs appear to be absent from postsynaptic sites: They are nonoverlapping with postsynaptic receptor clusters in the ganglion and are rapidly lost after ganglionic denervation. Similar pcdh-α patterns are found in motor axons and at neuromuscular junctions of birds and mammals, and persist into adulthood. The results indicate that pcdh-αs are widely expressed in nicotinic cholinergic pathways and may engage in heterophilic interactions at synapses and on axons.