Abstract
The δ1 glutamate receptor (GluD1) was cloned decades ago and is widely expressed in many regions of the brain. However, its functional roles in these brain circuits remain unclear. Here, we find that GluD1 is required for both excitatory synapse formation and maintenance in the hippocampus. The action of GluD1 is absent in the Cbln2 knockout mouse. Furthermore, the GluD1 actions require the presence of presynaptic neurexin 1β carrying the splice site 4 insert (+S4). Together, our findings demonstrate that hippocampal synapse assembly and maintenance require a tripartite molecular complex in which the ligand Cbln2 binds with presynaptic neurexin 1β (+S4) and postsynaptic GluD1. We provide evidence that this mechanism may apply to other forebrain synapses, where GluD1 is widely expressed.
Keywords:
Cbln2; GluD1; hippocampus; neurexin; synapse.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Brain / cytology
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Brain / metabolism
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Calcium-Binding Proteins
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Cell Differentiation / physiology
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Cells, Cultured
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Glutamate Dehydrogenase
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Hippocampus / cytology
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Hippocampus / metabolism*
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Mice
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Mice, Knockout
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neural Cell Adhesion Molecules / genetics
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Neural Cell Adhesion Molecules / metabolism*
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Neurons / cytology
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Neurons / metabolism
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Protein Precursors / genetics
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Protein Precursors / metabolism*
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Rats
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Receptors, Glutamate / genetics
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Receptors, Glutamate / metabolism*
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Synapses / genetics
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Synapses / metabolism*
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Synaptic Transmission
Substances
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Calcium-Binding Proteins
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Cbln2 protein, mouse
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Nerve Tissue Proteins
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Neural Cell Adhesion Molecules
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Nrxn1 protein, mouse
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Nrxn1 protein, rat
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Protein Precursors
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Receptors, Cell Surface
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Receptors, Glutamate
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glutamate receptor delta 1
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GluD1 protein, mouse
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Glutamate Dehydrogenase