関連する実験動画
Updated: Jun 22, 2026
10:24
Visualization of Endoplasmic Reticulum Localized mRNAs in Mammalian Cells
Published on: December 17, 2012
IRE1は,XBP-1mRNAを処理することによって,エンドプラズマ網膜の負荷を分泌能力に結び付けます
Marcella Calfon1, Huiqing Zeng, Fumihiko Urano
1Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
Nature
|January 10, 2002
まとめ
高級エウカリオットの展開タンパク質応答 (UPR) は,XBP-1 mRNAのIRE1依存のスプライシングによって調節される. このプロセスは,細胞がエンドプラズマ網膜のストレスに適応する上で極めて重要です.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- 展開タンパク質応答 (UPR) は,タンパク質の折り畳み能力を調節することによって,エンドプラズマ網膜 (ER) ホメオスタシスを維持します.
- 酵母では,HAC1 mRNAのIRE1媒介処理によってUPRが活性化され,Hac1転写因子の合成につながります.
- メタゾーンにおけるIRE1シグナル伝達経路は,特にUPR活性化におけるその役割に関して,あまり理解されていません.
研究 の 目的:
- メタゾーンにおけるUPRにおけるIRE1とXBP-1の役割を調査する.
- IRE1.1によるXBP-1 mRNA活性化のメカニズムを解明する.
- 高級ユカリオットにおけるER負荷調節の生理学的意義を理解する.
主な方法:
- Caenorhabditis elegans (ire-1およびxbp-1変異) の遺伝子ノックアウト研究.
- C. elegansとマウスにおけるUPR活性化への反応として,XBP-1 mRNAのスプライシングの分析.
- 精製されたマウスIRE1およびXBP-1mRNAを用いたインビトロ割れ分析.
主要な成果:
- ire-1 または xbp-1 の突然変異は,C. elegans. の UPR を廃止しました.
- C. elegansとマウスの両方におけるUPRの活性化により,XBP-1 mRNAのIRE1依存のスプライシングが誘発された.
- XBP-1タンパク質の蓄積は,UPR中のスプライスされたmRNAからのみ観察されました.
- マウス IRE1 は,XBP-1 mRNA を in vitro で直接切断し,直接の標的として特定しました.
結論:
- IRE1によるXBP-1mRNAスプライシングは,メタゾーンにおけるUPR活性化のための保存されたメカニズムである.
- この経路は,免疫グロブリン分泌などの特異的な分泌細胞機能に不可欠です.
- 生理学的ER負荷は,この調節機構を通じて,より高いエウカリオットの発達決定に影響を与えます.
関連する概念動画
01:17Role of ER in the Secretory Pathway
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
01:45ER Retrieval Pathway
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
01:34Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
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...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...