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Science 328 (5976): 363-368

Copyright © 2010 by the American Association for the Advancement of Science

Cbln1 Is a Ligand for an Orphan Glutamate Receptor {delta}2, a Bidirectional Synapse Organizer

Keiko Matsuda,1 Eriko Miura,1 Taisuke Miyazaki,2 Wataru Kakegawa,1 Kyoichi Emi,1 Sakae Narumi,1 Yugo Fukazawa,3 Aya Ito-Ishida,1,4 Tetsuro Kondo,1,5 Ryuichi Shigemoto,3 Masahiko Watanabe,2 Michisuke Yuzaki1,*

Abstract: Cbln1, secreted from cerebellar granule cells, and the orphan glutamate receptor {delta}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.

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}

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