Alpha-protocadherins are presynaptic and axonal in nicotinic pathways.

The protocadherin families pcdh-alpha, beta, and gamma have been proposed to mediate synaptic specificity via homophilic interactions. Here we report isolation of two pcdh-alpha family members from chick. We find pcdh-alpha 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-alphas in axons and perisynaptically in preganglionic terminals, adjacent to transmitter release sites. Pcdh-alphas 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-alpha patterns are found in motor axons and at neuromuscular junctions of birds and mammals, and persist into adulthood. The results indicate that pcdh-alphas are widely expressed in nicotinic cholinergic pathways and may engage in heterophilic interactions at synapses and on axons.