NMDA受容体のリン酸化をC端末ドメインの代替スプライシングによって調節する
W G Tingley1, K W Roche, A K Thompson
1Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Nature
|July 1, 1993
まとめ
NMDA受容体サブユニットNR1の代替スプライシングは,タンパク質キナーゼC (PKC) のリン酸化を調節する. このmRNAスプライシングメカニズムはグルタミン酸受容体の感受性に影響を与え,NR1を示唆している.
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:
- NMDA受容体は,シナプス可塑性などの脳機能に不可欠です.
- NMDA受容体のタンパク質リン酸化は,その活性を調節するために提案されています.
- NMDA受容体サブユニットNR1は,同類のサブユニットで構成されています.
研究 の 目的:
- タンパク質キナーゼC (PKC) によってNMDA受容体サブユニットNR1のリン酸化を調査する.
- NR1リン酸化における代替スプライシングの役割を決定する.
- NR1 C端末ドメインの細胞内局所化を調査する.
主な方法:
- 再結合NR1を発現する細胞におけるPKCによるNR1リン酸化を試験した.
- 主要な皮質ニューロン培養でNR1リン酸化を研究した.
- NR1リン酸化部位に対する代替スプライシングの影響を分析した.
主要な成果:
- PKCは複数の異なる部位でNR1をリン酸化する.
- 多くのリン酸化部位は,NR1のC端末領域の代替的にスプライスされたエクソン内に位置しています.
- NR1 mRNAの代替スプライシングは,そのPKCリン酸化を調節する.
結論:
- mRNAスプライシングは,グルタミン酸受容体のリン酸化に対する感受性を制御する新しいメカニズムです.
- NR1のC端領域は細胞内にある.
- グルタミン酸受容体のための提案されたトランスメブラントポロジーモデルは,改訂を必要とするかもしれません.
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