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The Journal of Neuroscience, June 15, 2003, 23(12):5096-5104
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 -Protocadherins Are Targeted to Subsets of Synapses and Intracellular Organelles in Neurons
Greg R. Phillips,1
Hidekazu Tanaka,3
Marcus Frank,1,4
Alice Elste,1
Lazar Fidler,1
Deanna L. Benson,1 and
David R. Colman1,2
1Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, 2Montreal Neurological Institute, Montreal, Quebec H3A 2B4, Canada, 3Department of Pharmacology, Osaka University School of Medicine, 2-2 Yamada-oka, Osaka, Japan, and 4Department of Molecular Embryology, Max-Planck Institute of Immunobiology, 79108 Freiburg, Germany
The clustered protocadherins (Pcdhs) comprise >50 putative synaptic recognition molecules that are related to classical cadherins and highly expressed in the nervous system. Pcdhs are organized into three gene clusters ( ,  , and  ). Within the and clusters, three exons encode the cytoplasmic domain for each Pcdh, making these domains identical within a cluster. Using an antibody to the Pcdh- constant cytoplasmic domain, we find that all interneurons in cultured hippocampal neurons express high levels of Pcdh-s in a nonsynaptic distribution. In contrast, only 48% of pyramidal-like cells expressed appreciable levels of these molecules. In these cells, Pcdh-s were associated with a subset of excitatory synapses in which they may mediate presynaptic to postsynaptic recognition in concert with classical cadherins. Immunogold localization in hippocampal tissue showed Pcdh-s at some synapses, in nonsynaptic plasma membranes, and in axonal and dendritic tubulovesicular structures, indicating that they may be exchanged among synapses and intracellular compartments. Our results show that although Pcdh-s can be synaptic molecules, synapses form lacking Pcdh-s. Thus, Pcdh-s and their relatives may be late additions to the classical cadherin-based synaptic adhesive scaffold; their presence in intracellular compartments suggests a role in modifying synaptic physiology or stability.
Key words: adhesion; synaptogenesis; postsynaptic density; pyramidal cells; interneurons; signaling
Received Nov. 12, 2002;
revised Apr. 10, 2003;
accepted Apr. 14, 2003.
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