Cbln1 is a ligand for an orphan glutamate receptor delta2, a bidirectional synapse organizer

Science. 2010 Apr 16;328(5976):363-8. doi: 10.1126/science.1185152.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / physiology*
  • Coculture Techniques
  • Excitatory Postsynaptic Potentials
  • Humans
  • Ligands
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Presynaptic Terminals / physiology
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Precursors / metabolism*
  • Purkinje Cells / metabolism
  • Purkinje Cells / physiology*
  • Rats
  • Receptors, Glutamate / chemistry
  • Receptors, Glutamate / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Synapses / physiology*
  • Synaptic Membranes / metabolism

Substances

  • Cbln1 protein, mouse
  • Ligands
  • Nerve Tissue Proteins
  • Protein Precursors
  • Receptors, Glutamate
  • Recombinant Fusion Proteins
  • glutamate receptor delta 2