光分解性ラパミシンの結合体で,小さなGTPaseの活性を空間時間的に制御する
Nobuhiro Umeda1, Tasuku Ueno, Christopher Pohlmeyer
1Department of Cell Biology, Center for Cell Dynamics, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Journal of the American Chemical Society
|December 15, 2010
まとめ
科学者たちは,光を用いた信号分子を制御するための新しい方法を開発しました. この技術は,Racのようなタンパク質の精密な細胞下活性化を可能にし,ダイナミックな細胞内信号伝達の研究を支援します.
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:
- 細胞内信号伝達経路は,細胞機能にとって極めて重要です.
- 信号分子の空間時間的活動を制御することは,細胞のプロセスを理解するために不可欠です.
- 信号分子の活動を制御するための既存の方法は,精度と範囲の制限があります.
研究 の 目的:
- 信号分子活動の空間時間的な制御のための新しい方法を開発する.
- 信号分子の細胞下局的活性化を達成するために.
- ダイナミックな細胞内信号イベントの正確な調査を可能にするために.
主な方法:
- 新型フォトケージラパミシン誘導体の合成.
- 紫外線照射を用いて,FKBPとFRBのタンパク質の二酸化を誘発する.
- ターゲットを絞った活性化のために,空間的に制限された紫外線照射を使用します.
- 小型GTPasesの活性化,特にRac.
主要な成果:
- フォトケージラパミシン誘導体は,FKBPとFRBのUV曝露時の急速な二酸化を可能にしました.
- 空間的に限定された紫外線照射は, Rac.の細胞下局所的活性化につながった.
- 細胞内シグナル伝達分子の活性化を正確に制御することが実証されています.
結論:
- 開発されたフォトケージラパミシンシステムは,信号伝達の空間時間的な制御のための強力なツールを提供します.
- この技術は,細胞内のタンパク質の高度な局所的活性化を可能にします.
- 高解像度でダイナミックな細胞内シグナル伝達イベントを研究するための重要な進歩を提供します.
関連する概念動画
02:14GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:14Rab 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...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
01:25Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.