title: Cbln1 is a ligand for an orphan glutamate receptor delta2, a bidirectional synapse organizer.
abstract: Cbln1, secreted from cerebellar granule cells, and the orphan glutamate receptor delta2 (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.
authors.affiliation: Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuda
authors.forename: Eriko
authors.initials: E
authors.lastname: Miura
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Kakegawa
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Emi
authors.forename: Sakae
authors.initials: S
authors.lastname: Narumi
authors.forename: Yugo
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Aya
authors.initials: A
authors.lastname: Ito-Ishida
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kondo
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D018920:Coculture Techniques; D019706:Excitatory Postsynaptic Potentials; D006801:Humans; D008024:Ligands; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000502:physiology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011498:Protein Precursors / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017470:Receptors, Glutamate / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D013570:Synaptic Membranes / Q000378:metabolism
chemical_list: C092370:Cbln1 protein, mouse; D008024:Ligands; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017470:Receptors, Glutamate; D011993:Recombinant Fusion Proteins; C107913:glutamate receptor delta 2