Gamma-protocadherins are targeted to subsets of synapses and intracellular organelles in neurons.
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 (alpha, beta, and gamma). Within the alpha and gamma clusters, three exons encode the cytoplasmic domain for each Pcdh, making these domains identical within a cluster. Using an antibody to the Pcdh-gamma constant cytoplasmic domain, we find that all interneurons in cultured hippocampal neurons express high levels of Pcdh-gamma(s) in a nonsynaptic distribution. In contrast, only 48% of pyramidal-like cells expressed appreciable levels of these molecules. In these cells, Pcdh-gamma(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-gamma(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-gamma(s) can be synaptic molecules, synapses form lacking Pcdh-gamma(s). Thus, Pcdh-gamma(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.
Phillips
Greg R
GR
Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Tanaka
Hidekazu
H
Frank
Marcus
M
Elste
Alice
A
Fidler
Lazar
L
Benson
Deanna L
DL
Colman
David R
DR
D017398:Alternative Splicing; D000818:Animals; D000918:Antibody Specificity; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D005968:Glutamate Decarboxylase; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins; D009419:Nerve Tissue Proteins; C033652:postsynaptic density proteins; D005968:Glutamate Decarboxylase