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 bi-directionally on both pre- and postsynapticcomponents. This study was conducted by Keio University (Prof. Yuzaki Lab) in collaboration with Hokkaido University (Prof. Watanabe Lab) and NIPS (Prof. Shigemoto Lab), and supported by NIPS “Planned collaborative project”.
