The extreme C-terminus of GluRδ2 is essential for induction of long-term depression in cerebellar slices

Kazuhisa Kohda, Wataru Kakegawa, Shinji Matsuda, Ryoichi Nakagami, Naomasa Kakiya, Michisuke Yuzaki

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Long-term depression (LTD) of parallel fibre (PF)-Purkinje cell synapses in the cerebellum is recognized as a cellular substrate of motor learning. Although the δ2 glutamate receptor (GluRδ2) has been shown to be crucial for LTD, the mechanisms by which GluRδ2 functions remain elusive. In this study, we developed a virus vector-based gene transfer approach to rescue impaired LTD in GluRδ2-null Purkinje cells in cerebellar slice preparations. We demonstrated that LTD was restored in GluRδ2-null Purkinje cells transduced with wild-type but not with mutant GluRδ2, which lacked the PDZ-ligand domain in the C-terminus. Immunohistochemical analysis revealed no difference in expression levels or spine localization patterns between virally introduced wild-type and mutant GluRδ2 proteins. Similarly, LTD was abrogated in Purkinje cells that had been acutely perfused with peptides, hampering the interaction of GluRδ2 with PDZ proteins such as PSD-93, PTPMEG and S-SCAM but not with delphilin. Together, these results indicate that PDZ proteins that bind to the C-terminus of GluRδ2 are not essential for localizing GluRδ2 at synapses but are crucial for conveying signals necessary for the induction of LTD.

Original languageEnglish
Pages (from-to)1357-1362
Number of pages6
JournalEuropean Journal of Neuroscience
Volume25
Issue number5
DOIs
Publication statusPublished - 2007 Mar

Fingerprint

Purkinje Cells
Depression
Null Lymphocytes
Synapses
PDZ Domains
Glutamate Receptors
Mutant Proteins
Cerebellum
Proteins
Spine
Learning
Ligands
Viruses
Peptides
Genes

Keywords

  • Cerebellum
  • Glutamate receptor
  • Long-term depression
  • Purkinje cell
  • Sindbis virus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The extreme C-terminus of GluRδ2 is essential for induction of long-term depression in cerebellar slices. / Kohda, Kazuhisa; Kakegawa, Wataru; Matsuda, Shinji; Nakagami, Ryoichi; Kakiya, Naomasa; Yuzaki, Michisuke.

In: European Journal of Neuroscience, Vol. 25, No. 5, 03.2007, p. 1357-1362.

Research output: Contribution to journalArticle

Kohda, Kazuhisa ; Kakegawa, Wataru ; Matsuda, Shinji ; Nakagami, Ryoichi ; Kakiya, Naomasa ; Yuzaki, Michisuke. / The extreme C-terminus of GluRδ2 is essential for induction of long-term depression in cerebellar slices. In: European Journal of Neuroscience. 2007 ; Vol. 25, No. 5. pp. 1357-1362.
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