期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 10, 页码 E948-E957出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1218380110
关键词
synaptic plasticity; mouse
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Keio Gijuku Academic Development Funds
- Keio University Medical Science Fund
- Research Grants for Life Science and Medicine
- Naito Foundation
- Inamori Foundation
- Nakajima Foundation
- Takeda Science Foundation
- Precursory Research for Embryonic Science and Technology (PRESTO) program from the Japan Science and Technology Agency (JST)
- Core Research for Evolutional Science and Technology (CREST) from the JST
- Grants-in-Aid for Scientific Research [21229006, 23689012, 23500399] Funding Source: KAKEN
Long-term depression (LTD) commonly affects learning and memory in various brain regions. Although cerebellar LTD absolutely requires the delta 2 glutamate receptor (GluD2) that is expressed in Purkinje cells, LTD in other brain regions does not; why and how cerebellar LTD is regulated by GluD2 remains unelucidated. Here, we show that the activity-dependent phosphorylation of serine 880 (S880) in GluA2 AMPA receptor subunit, which is an essential step for AMPA receptor endocytosis during LTD induction, was impaired in GluD2-null cerebellum. In contrast, the basal phosphorylation levels of tyrosine 876 (Y876) in GluA2 were increased in GluD2-null cerebellum. An in vitro phosphorylation assay revealed that Y876 phosphorylation inhibited subsequent S880 phosphorylation. Conversely, Y876 dephosphorylation was sufficient to restore S880 phosphorylation and LTD induction in GluD2-null Purkinje cells. Furthermore, megakaryocyte protein tyrosine phosphatase (PTPMEG), which binds to the C terminus of GluD2, directly dephosphorylated Y876. These data indicate that GluD2 gates LTD by coordinating interactions between the two phosphorylation sites of the GluA2.
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