インテグリンは,膜ドメインの内部化によってRacターゲティングを調節する
Miguel A del Pozo1, Nazilla B Alderson, William B Kiosses
1Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. mdelpozo@scripps.edu
まとめ
細胞粘着は,コレステロールに富んだ膜領域を制御することによって,Rac1タンパク質の活性を調節する. インテグリン信号と脂質ラフト調節は,Rac1の鍵です.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- Rac1のプラズマ膜への転位は,下流効果器の活性化に不可欠である.
- Rac1の活性化には,細胞外マトリックスへのインテグリン媒介の細胞結合が必要である.
研究 の 目的:
- Rac1転位における膜脂質と脂質ラフトの役割を調査する.
- 細胞粘着が膜ドメインダイナミクスを通してRac1の活動をどのように調節するかを理解する.
主な方法:
- 活性Rac1が異なる膜組成に結合する好みを研究した.
- 血コレステロールと脂質ラフトマーカーの細胞脱離の影響を調査した.
- Rac1膜ターゲティングとエフェクタアクティベーションに対する脂質ラフト内化防止の影響を調査した.
主要な成果:
- アクティブRac1は,好ましくは低密度でコレステロールが豊富な膜に結合する.
- 細胞分離は,血コレステロールと脂質ラフトマーカーの内部化を誘導する.
- リピッド・ラフト・インターナライゼーションの阻害は,非粘着性細胞におけるRac1膜ターゲティングとエフェクター活性化を維持する.
結論:
- 膜脂質の組成,特にコレステロールの含有量は,Rac1の局所化に影響します.
- インテグリンシグナル伝達は,脂質ラフトのダイナミクスを調節し,アデレント細胞のRac1活動を制御します.
- リピッド・ラフト・レギュレーションをターゲットにすることで,Rac1に依存したシグナル伝達経路を調節する潜在的な戦略が提供されます.
関連する概念動画
Regulated mRNA Transport
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...
Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Directing 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...
Protein Modifications in the RER
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Cell Polarization by Rho Proteins
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...


