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 journalArticle

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

Fingerprint

Serine
Protein Kinase C
Purkinje Cells
Phosphorylation
Depression
Synapses
Glutamate Receptors
Cerebellum
Sindbis Virus
Null Lymphocytes
Neuronal Plasticity
Protein S
Synaptic Transmission
Alanine
glutamate receptor delta 2
Learning

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression. / Nakagami, Ryoichi; Kohda, Kazuhisa; Kakegawa, Wataru; Kondo, Tetsuro; Kato, Nobumasa; Yuzaki, Michisuke.

In: Keio Journal of Medicine, Vol. 57, No. 2, 06.2008, p. 105-110.

Research output: Contribution to journalArticle

Nakagami, Ryoichi ; Kohda, Kazuhisa ; Kakegawa, Wataru ; Kondo, Tetsuro ; Kato, Nobumasa ; Yuzaki, Michisuke. / Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression. In: Keio Journal of Medicine. 2008 ; Vol. 57, No. 2. pp. 105-110.
@article{701212e91b6543628e69342dfab6dd7d,
title = "Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression",
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.",
keywords = "δ2 glutamate receptor, Cerebellum, Long-term depression, Phosphorylation, Purkinje cell",
author = "Ryoichi Nakagami and Kazuhisa Kohda and Wataru Kakegawa and Tetsuro Kondo and Nobumasa Kato and Michisuke Yuzaki",
year = "2008",
month = "6",
doi = "10.2302/kjm.57.105",
language = "English",
volume = "57",
pages = "105--110",
journal = "Keio Journal of Medicine",
issn = "0022-9717",
publisher = "Keio University School of Medicine",
number = "2",

}

TY - JOUR

T1 - Phosphorylation of delta2 glutamate receptors at serine 945 is not required for cerebellar long-term depression

AU - Nakagami, Ryoichi

AU - Kohda, Kazuhisa

AU - Kakegawa, Wataru

AU - Kondo, Tetsuro

AU - Kato, Nobumasa

AU - Yuzaki, Michisuke

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

KW - δ2 glutamate receptor

KW - Cerebellum

KW - Long-term depression

KW - Phosphorylation

KW - Purkinje cell

UR - http://www.scopus.com/inward/record.url?scp=47249132139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47249132139&partnerID=8YFLogxK

U2 - 10.2302/kjm.57.105

DO - 10.2302/kjm.57.105

M3 - Article

VL - 57

SP - 105

EP - 110

JO - Keio Journal of Medicine

JF - Keio Journal of Medicine

SN - 0022-9717

IS - 2

ER -