NMDA受容体のNR1サブユニットの調節された細胞下分布
M D Ehlers1, W G Tingley, R L Huganir
1Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Science (New York, N.Y.)
|September 22, 1995
まとめ
N-メチル-D-アスパルテート (NMDA) 受容体
科学分野:
- 神経科学は神経科学である.
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- N-メチル-D-アスパルテート (NMDA) 受容体は,哺乳類の脳における刺激性シナプス伝達に不可欠である.
- NMDA受容体の正確な局所化メカニズムを理解することは,シナプス機能を理解するための鍵です.
- 以前の研究は,シナプス標的化における特定の受容体サブユニットの重要性を示しています.
研究 の 目的:
- NMDA受容体のポストシナプス局所化に起因する分子機構を調査する.
- 特定のタンパク質ドメインと,NMDA受容体密輸とアンカリングに関与する規制要因を特定する.
主な方法:
- 線維芽細胞細胞系におけるNMDA受容体NR1サブユニット・スプライス・バリエーションの発現.
- 免疫光顕微鏡を用いた受容体局在性の分析.
- AMPA受容体に特定のエクソンカセットを挿入する機能的研究.
- タンパク質キナーゼCのリン酸化が受容体の局所化に及ぼす影響に関する研究.
主要な成果:
- NMDA受容体NR1スプライス変種で,最初のCOOH末端エクソンカセットは,離散的なプラズマ膜ドメインに局所されています.
- このエクソンカセットが欠けていたNR1変種は,拡散した細胞内分布を示した.
- 特定されたエクソンカセットは,GluR1 AMPA受容体に局所化を授与するのに十分でした.
- タンパク質キナーゼCのリン酸化は,これらの受容体豊富な膜領域を破壊した.
結論:
- NMDA受容体NR1サブユニット内の特定のアミノ酸配列は,その局所化を離散的な膜領域に決定する.
- NR1サブユニットの代替スプライシングは,そのサブセルラーターゲティングを決定的に調節します.
- タンパク質のリン酸化,特にタンパク質キナーゼCによって,NMDA受容体の局所化を調節する.
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