エンドプラズマ網膜からの劣化:新合成タンパク質の廃棄
J Lippincott-Schwartz1, J S Bonifacino, L C Yuan
1Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Cell
|July 15, 1988
まとめ
新しく合成されたT細胞受容体 (TCR) サブユニットは,エンドプラズマ網膜 (ER) にリンクされた前ゴルギ経路を通じて急速に分解されます. このERに関連した分解経路は,細胞から不完全なタンパク質複合体を除去します.
科学分野:
- 細胞生物学 細胞生物学
- 免疫学 免疫学とは
- タンパク質の分解
背景:
- 新しく合成されたT細胞受容体 (TCR) のサブユニットは,機能するために適切な組み立てを必要とします.
- タンパク質の分解経路は,細胞ホメオスタシスと品質管理に不可欠です.
研究 の 目的:
- T細胞受容体 (TCR) サブユニットの分解に関与する新しいタンパク質分解経路の特徴づけ.
- この分解経路の細胞の位置と特性を決定する.
主な方法:
- タンパク質の分解運動を研究するための生化学的分析.
- 腐敗部位を特定するための形態学的技術.
- TCR輸送を妨害するためにイオノフォアの使用.
- 感染した線維芽細胞とT細胞におけるTCRサブユニット分解の分析.
主要な成果:
- ゲルギ前,エンドプラズマ網膜 (ER) に関連した分解経路は,新たに合成されたTCRサブユニットを急速に分解します.
- この経路はリソソーム分解とは異なるもので,ER-to-Golgi輸送が遮断された場合でも動作します.
- ER経路は,組み立てられていないTCRアルファ鎖とアルファ-ベータ複合体を分解する主な経路です.
- 新しく合成されたすべてのTCRアルファ,ベータ,デルタ鎖は,イオノフォールで処理されたT細胞で,この経路で分解されます.
結論:
- ERに関連した分解経路は,分泌経路から誤って組み立てられた膜タンパク質複合体を除去する上で重要な役割を果たします.
- この経路は,T細胞受容体 (TCR) の構成と機能の品質管理に不可欠です.
関連する概念動画
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02:11Proteins: From Genes to Degradation
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01:37The Unfolded Protein Response
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01:27Post-translational Translocation of Proteins to the RER
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
01:32Export of Misfolded Proteins out of the ER
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
02:11Proteins: From Genes to Degradation
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA molecules by RNA...
Transcription is the synthesis of RNA molecules by RNA...