"ゲーティング・チャージ"の動きは,Gタンパク質結合受容体のリガンド結合と結合する
Yair Ben-Chaim1, Baron Chanda, Nathan Dascal
1Department of Neurobiology, The Hebrew University, Jerusalem, 91904, Israel.
Nature
|October 27, 2006
まとめ
Gタンパク質結合受容体 (GPCRs) は通常,電圧感受性とはみなされない. この研究では,GPCRsは,マスカリン受容体と同様に,内在的に膜ポテンシャルを感知し,アゴニスト結合に影響を及ぼすことを示す電荷の動きを示していることが明らかになりました.
科学分野:
- バイオケミストリー バイオケミストリー
- 細胞生物学 細胞生物学
- 神経科学は神経科学である.
背景:
- Gタンパク質結合受容体 (GPCRs) は,重要な細胞信号伝達経路を媒介する.
- GPCRは膜タンパク質であるが,伝統的に電圧感受性とは考えられていない.
- 最近の発見は,膜ポテンシャルがGPCR活性とアゴニストの親和性に影響を及ぼすことを示唆しています.
研究 の 目的:
- GPCRsが膜ポテンシャルの変化に内在的に反応するかどうかを調査する.
- GPCRにおける電圧感知メカニズムを特徴づける.
- 電圧感知と信号伝達の結合における特定の受容器領域の役割を明らかにする.
主な方法:
- 電気生理学的記録は,ムスカリン受容体 (m2Rとm1R) の電荷移動 (ゲーティング電流) を検出する.
- m2R. の電荷-電圧関係の分析.
- Gタンパク質結合ループに焦点を当てたミュータゲネシスの研究.
主要な成果:
- 2つの原型GPCRであるm2およびm1マスカリン受容体 (m2Rおよびm1R) は,電圧ゲートチャネルに似た,電荷移動に関連した電流を示します.
- m2Rのゲーティング電荷-電圧関係は,アセチルコリンに対する電圧依存の親和性に一致します.
- Gタンパク質結合ループは,電圧感知とアゴニスト結合親和を結びつけるのに不可欠です.
結論:
- GPCRには固有の電圧感知能力があります.
- トランスメブランポテンシャルは,化学信号とともに,GPCRsの規制信号として作用します.
- GPCRは,電気的刺激と化学的刺激の両方のダブルセンサとして機能します.
関連する概念動画
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
G Protein-coupled Receptors
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...


