Cbln1 is a ligand for an orphan glutamate receptor delta2, a bidirectional synapse organizer.
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.
Matsuda
Keiko
K
Department of Physiology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Miura
Eriko
E
Miyazaki
Taisuke
T
Kakegawa
Wataru
W
Emi
Kyoichi
K
Narumi
Sakae
S
Fukazawa
Yugo
Y
Ito-Ishida
Aya
A
Kondo
Tetsuro
T
Shigemoto
Ryuichi
R
Watanabe
Masahiko
M
Yuzaki
Michisuke
M
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
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