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ER Retrieval Pathway01:45

ER Retrieval Pathway

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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...
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Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

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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...
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Clathrin Coated Vesicles01:12

Clathrin Coated Vesicles

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Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
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Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

7.2K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
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Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

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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...
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Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

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Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
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Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
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レトロマー複合体による貨物の認識のための構造的メカニズム

María Lucas1, David C Gershlick2, Ander Vidaurrazaga1

  • 1Structural Biology Unit, CIC bioGUNE, Bizkaia Technology Park, 48160 Derio, Spain.

Cell
|November 28, 2016
PubMed
まとめ
この要約は機械生成です。

レトロマータンパク質複合体の機能障害は神経変性疾患に関連しています. この研究はレトロマーが 荷物を認識する方法を明らかにし 細胞のリサイクルと病気のメカニズムを理解する上で 重要なステップです

キーワード:
貨物の認識エンドサイトリサイクルエンドソーム膜の募集膜チューブルプロテインコート逆行輸送レトロマーネクシンを分類する配列シグナル

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Förster Resonance Energy Transfer Mapping: A New Methodology to Elucidate Global Structural Features
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Live-cell Imaging of Endocytic Transport using Functionalized Nanobodies in Cultured Cells
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科学分野:

  • 細胞生物学
  • 構造生物学
  • 神経科学

背景:

  • レトロメアは,トランスメブランタンパク質のリサイクルを担当する重要なマルチタンパク質複合体です.
  • 機能不全のレトロマーが アルツハイマー病やパーキンソン病に 関わっている.
  • レトロマー貨物の認識とエンドソーマル募集のメカニズムは不明である.

研究 の 目的:

  • レトロマー貨物の認識と膜採用の構造的基礎を解明する.
  • レトロマーサブユニットSNX3と貨物の相互作用を調査する

主な方法:

  • 4つの構成要素を分析するためにX線結晶学を用いた.
  • コンプレックスにはVPS26,VPS35,SNX3とDMT1-IIリサイクル信号が含まれていた.

主要な成果:

  • リサイクル信号のための新しい結合部位は,VPS26-SNX3インターフェイスで特定されました.
  • レトロマーサブユニットSNX3と貨物の間の協力的相互作用が明らかになった.
  • これらの相互作用は,貨物信号の認識と膜の採用を結びつける.

結論:

  • この研究は,レトロメアの貨物認識メカニズムに関する構造的な洞察を提供します.
  • これらの相互作用を理解することは,病気におけるレトロマー機能障害に対処するために不可欠です.
  • この研究は,レトロマーを標的とした将来の治療戦略の基礎となる.