Epsin1は,クラトリン媒介性内細胞症の間に,どこにでも存在する貨物の凝縮に依存するチェックポイントを強制する
Susovan Sarkar1, Hao-Yang Liu1, Feng Yuan1
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
Nature communications
|August 25, 2025
まとめ
エプシン1は,ユビキティラートされた荷物が存在する場合にのみ,イニシアタータンパク質凝縮体を安定させることで,クラトリン媒介性内細胞症のチェックポイントとして作用する. これは特定の細胞の構成要素の効率的な内部化を保証します.
科学分野:
- 細胞生物学
- 分子生物学
- 生物化学
背景:
- クラトリン媒介の内細胞化は,細胞表面のタンパク質と脂質の内部化に不可欠です.
- イニシアタータンパク質の 柔軟な凝縮物によって クラスリンで覆われた小胞が 種間で組み合わされます
研究 の 目的:
- エプシン1が,エンドサイトーシス中のイニシアタータンパク質凝縮体を調節する役割を調査する.
- Epsin1がどのように cargoに依存する内細胞チェックポイントを作り出しているのかを理解するためにです.
主な方法:
- タンパク質凝縮の動態を評価する in vitro 生化学的測定法
- 哺乳類の細胞での実験 遺伝子操作による内細胞機能の評価
- イニシアタータンパク質とのエプシン1とウビキチン相互作用の分析
主要な成果:
- エプシン1は,ウビキチンなしではイニシアタータンパク質の凝縮を不安定化しますが,ポリウビキチンがあれば安定化します.
- 哺乳類の細胞内細胞化は,ユビキチンまたはエプシン1の欠如によって損なわれます.
- UbiquitinとEpsin1の両方の同時除去は,荷重選択性の損失があるものの,内細胞的欠陥を大きく救う.
結論:
- Epsin1はタンパク質の凝縮を動的に調整して, どこにでも存在する荷物の内部化を促進します.
- このメカニズムは,分子相互作用が細胞の出来事を制御し,負荷に依存する内細胞のチェックポイントを確立することを強調しています.
関連する概念動画
Protein Folding Quality Check in the RER
3.8K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.8K
Regulation of the Unfolded Protein Response
2.6K
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...
2.6K
Tail-anchoring of Proteins in the ER Membrane
3.2K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.2K
Export of Misfolded Proteins out of the ER
3.9K
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...
3.9K
Coat Assembly and GTPases
3.6K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.6K
ER Retrieval Pathway
3.9K
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...
3.9K


