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Abstract:
Cbln1, secreted from cerebellar granule cells, and the orphanglutamate receptor 2 (GluD2), expressed by Purkinje cells, areessential for synapse integrity between these neurons in adultmice. Nevertheless, no endogenous binding partners for thesemolecules have been identified. We found that Cbln1 binds directlyto the N-terminal domain of GluD2. GluD2 expression by postsynapticcells, combined with exogenously applied Cbln1, was necessaryand sufficient to induce new synapses in vitro and in the adultcerebellum in vivo. Further, beads coated with recombinant Cbln1directly induced presynaptic differentiation and indirectlycaused clustering of postsynaptic molecules via GluD2. Theseresults indicate that the Cbln1-GluD2 complex is a unique synapseorganizer that acts bidirectionally on both pre- and postsynapticcomponents.
1 Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan. 2 Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. 3 Division of Cerebral Structures, National Institutes for Physiological Sciences, Okazaki 444-8787, Japan. 4 Department of Cellular Neurobiology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan. 5 Molecular Neurophysiology, Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8566, Japan.
* To whom correspondence should be addressed. E-mail: myuzaki{at}a5.keio.jp
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Bridging the Synaptic Cleft: Lessons from Orphan Glutamate Receptors.
2, a Bidirectional Synapse Organizer
2 (GluD2), expressed by Purkinje cells, are essential for synapse integrity between these neurons in adult mice. Nevertheless, no endogenous binding partners for these molecules have been identified. We found that Cbln1 binds directly to the N-terminal domain of GluD2. GluD2 expression by postsynaptic cells, combined with exogenously applied Cbln1, was necessary and sufficient to induce new synapses in vitro and in the adult cerebellum in vivo. Further, beads coated with recombinant Cbln1 directly induced presynaptic differentiation and indirectly caused clustering of postsynaptic molecules via GluD2. These results indicate that the Cbln1-GluD2 complex is a unique synapse organizer that acts bidirectionally on both pre- and postsynaptic components. 
