New (but old) molecules regulating synapse integrity and plasticity: Cbln1 and the δ2 glutamate receptor

Research output: Contribution to journalArticle

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Abstract

The δ2 glutamate receptor (GluRδ2) is predominantly expressed in cerebellar Purkinje cells and plays crucial roles in cerebellar functions: GluRδ2-null mice display ataxia and impaired motor learning. Interestingly, the contact state of synapses between parallel fibers (PFs) and Purkinje cells is specifically and severely affected, and the number of normal PF synapses is markedly reduced in GluRδ2-null Purkinje cells. Furthermore, long-term depression at PF-Purkinje cell synapses is abrogated. Cbln1, a member of the C1q/tumor necrosis factor (TNF) superfamily, is predominantly expressed and released from cerebellar granule cells. Unexpectedly, the behavioral, physiological and anatomical phenotypes of cbln1-null mice precisely mimic those of GluRδ2-null mice. Thus, we propose that Cbln1, which is released from granule cells, and GluRδ2, which is predominantly expressed in Purkinje cells, are involved in a common signaling pathway crucial for synapse formation/maintenance and plasticity in the cerebellum. Since molecules related to Cbln1 are expressed in various brain regions other than the cerebellum, other C1q/TNF superfamily proteins may also regulate various aspects of synapses in the CNS. Therefore, an understanding of the signaling mechanisms underlying Cbln1 and GluRδ2 in the cerebellum will provide new insights into the roles of C1q/TNF superfamily proteins as new cytokines that regulate normal and abnormal brain functions.

Original languageEnglish
Pages (from-to)633-643
Number of pages11
JournalNeuroscience
Volume162
Issue number3
DOIs
Publication statusPublished - 2009 Sep 1

Fingerprint

Purkinje Cells
Glutamate Receptors
Synapses
Cerebellum
Tumor Necrosis Factor-alpha
Null Lymphocytes
Brain
Ataxia
Proteins
Maintenance
Learning
Depression
Cytokines
Phenotype

Keywords

  • C1q
  • cerebellum
  • LTD
  • parallel fiber
  • Purkinje cell
  • synapse formation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

New (but old) molecules regulating synapse integrity and plasticity : Cbln1 and the δ2 glutamate receptor. / Yuzaki, Michisuke.

In: Neuroscience, Vol. 162, No. 3, 01.09.2009, p. 633-643.

Research output: Contribution to journalArticle

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