Cbln1 and the delta2 glutamate receptor - An orphan ligand and an orphan receptor find their partners

Research output: Contribution to journalReview articlepeer-review

17 Citations (Scopus)


Cerebellin was originally discovered as a Purkinje cell-specific peptide more than two decades ago. Later, its precursor protein precerebellin (Cbln1) was found to be produced in cerebellar granule cells. It has become increasingly clear that although the cerebellin peptide may have certain functions, Cbln1 is an actual signaling molecule that belongs to the C1q family. However, the precise function of Cbln1 has been unresolved. Cbln1 is released from granule cells, and disruption of the cbln1 gene in mice causes a severe reduction in the number of synapses between Purkinje cells and parallel fibers (PFs; axons of granule cells) and results in cerebellar ataxia. The glutamate receptor δ2 (GluD2) is highly expressed on Purkinje cells' dendritic spines which make synapses with PFs. Although GluD2 was identified as a member of the ionotropic glutamate receptors more than 15 years ago, it has been referred to as an orphan receptor because its endogenous ligands are unclear. Interestingly, GluD2-null mice phenocopy cbln1-null mice precisely. Cbln1 and GluD2 have therefore been thought to participate in a common signaling pathway that is required for the formation of PF synapses. We recently established a direct ligand-receptor relationship between Cbln1 and GluD2. The Cbln1-GluD2 complex is located at the cleft of PF-Purkinje cell synapses and bidirectionally regulates both presynaptic and postsynaptic differentiation.

Original languageEnglish
Pages (from-to)78-84
Number of pages7
Issue number1
Publication statusPublished - 2012 Mar


  • Cerebellin
  • Cerebellum
  • Granule cell
  • Parallel fiber
  • Synapse formation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Cbln1 and the delta2 glutamate receptor - An orphan ligand and an orphan receptor find their partners'. Together they form a unique fingerprint.

Cite this