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関連する概念動画

IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.7K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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GPCR Desensitization01:12

GPCR Desensitization

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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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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...
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関連する実験動画

Updated: Aug 22, 2025

Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
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膜フォスフォノシチドは,GPCR-β-アレスティン複合体の構成と動態を調節する.

John Janetzko1, Ryoji Kise2, Benjamin Barsi-Rhyne3

  • 1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Cell
|November 11, 2022
PubMed
まとめ

膜フォスフォノシチド (PIP) は,アストリンがGタンパク質結合受容体 (GPCR) に結合する方法を制御する. PIPはGPCR-アレスティン複合体を安定させ,受容体のシグナル伝達とリサイクルに影響を与えます.

キーワード:
GPCR についてアレストイン構成動態エンドサイトーシス光スペクトロシーフォスフォノシチドシグナリング

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Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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科学分野:

  • 細胞生物学
  • 生物化学
  • 分子薬理学

背景:

  • アレスティンがリン酸化Gタンパク質結合受容体 (GPCRs) に結合することは,信号調節に不可欠である.
  • β-アレスティンのインパクトシグナル伝達とリサイクル経路によるGPCR内化ダイナミクス.
  • 膜フォスフォノシチド (PIP) は,GPCR-β-アレスティンの相互作用の調節に関与しています.

研究 の 目的:

  • β-アレスティン募集とGPCR-β-アレスティン複合体のダイナミクスにおける膜フォスフォノシチド (PIP) の役割を調査する.
  • PIPがGPCRとβ-アレスティンの相互作用にどのように影響するかを決定する.
  • PIPの相互作用に基づいてGPCRのシグナル伝達とリサイクルを制御するメカニズムを理解する.

主な方法:

  • GPCR-β-アレスティンの相互作用を研究するために,細胞ベースの測定法を使用した.
  • 複雑なダイナミクスを分析するために in vitro 生物物理的測定法を使用します.
  • 膜フォスフォノシチドがアスタシン募集に及ぼす影響を調査した.

主要な成果:

  • GPCRは,β-アレスティンの徴用のためのPIP結合の必要性に基づいて2つのグループに分類されました.
  • プラズマ膜PIPは活性β-アレスティン構造を強化し,GPCR-β-アレスティン複合体を安定させることが判明した.
  • PIPはアロステル変調剤として作用し,GPCR-β-アレスティン複合体の構成多様性を可能にします.

結論:

  • 膜PIPは,GPCR-β-アレスティンの相互作用のダイナミクスを調節する上で重要な役割を果たします.
  • GPCRの運命を影響する,β-アレスティンの募集のためのPIP依存および独立した経路が存在する.
  • PIPは,β-アレスティンの放出と,その後のGPCRのリサイクルのためのメカニズムを提供します.