Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression

Ryoichi Nakagami, Kazuhisa Kohda, Wataru Kakegawa, Tetsuro Kondo, Nobumasa Kato, Michisuke Yuzaki

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Long-term depression (LTD) of synaptic transmission at parallel fiber (PF)-Purkinje cell synapses is thought to regulate motor learning and memory formation in the cerebellum. Neuronal activity-evoked protein kinase C (PKC) activation is required for the induction of LTD. In addition, the δ2 glutamate receptor (GluRδ2), which is predominantly expressed at PF-Purkinje cell synapses, is indispensable for the induction of LTD; however, the mechanisms by which GluRδ2 regulates LTD and its relationship with PKC activation remain elusive. Interestingly, GluRδ2 is phosphorylated by PKC on serine 945 (Ser945) near its C-terminus and a postsynaptic protein S-SCAM, which could potentially regulate glutamate receptor trafficking and synaptic plasticity, binds to the extreme C-terminus of GluRδ2 in a phosphorylation-dependent manner on Ser945. Here, using a Sindbis-based virus expression approach, we show that a mutant GluRδ2, in which alanine replaced Ser945 and did not undergo PKC phosphorylation, was normally localized at the postsynaptic sites of PF-Purkinje cell synapses. In addition, like wild-type GluRδ2, the phosphorylation-disrupted GluRδ2 successfully rescued abrogated LTD in GluRδ2-null Purkinje cells. These results indicate that Ser945, a major PKC phosphorylation site of of GluRδ2, may not play a crucial role in induction of LTD in the cerebellum.

Original languageEnglish
Pages (from-to)105-110
Number of pages6
JournalKeio Journal of Medicine
Volume57
Issue number2
DOIs
Publication statusPublished - 2008 Jun

Keywords

  • Cerebellum
  • Long-term depression
  • Phosphorylation
  • Purkinje cell
  • δ2 glutamate receptor

ASJC Scopus subject areas

  • Medicine(all)

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