New (but old) molecules regulating synapse integrity and plasticity: Cbln1 and the delta2 glutamate receptor

Neuroscience
Michisuke Yuzaki

Abstract

The delta2 glutamate receptor (GluRdelta2) is predominantly expressed in cerebellar Purkinje cells and plays crucial roles in cerebellar functions: GluRdelta2-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 GluRdelta2-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 GluRdelta2-null mice. Thus, we propose that Cbln1, which is released from granule cells, and GluRdelta2, 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, ...Continue Reading

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Citations

Apr 5, 2011·Nature Neuroscience·Wataru KakegawaMichisuke Yuzaki
Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Kazuhisa KohdaMichisuke Yuzaki
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Feb 25, 2014·Communicative & Integrative Biology·Kazuhisa KohdaMichisuke Yuzaki
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May 28, 2019·The Cerebellum·Sheng-Han KuoRodger J Elble
Oct 6, 2018·Proceedings of the National Academy of Sciences of the United States of America·Erica SeigneurThomas C Südhof

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