TPCタンパク質は,エンドソームとリソソームのフォスホイノシチド活性化ナトリウム選択イオンチャンネルです
Xiang Wang1, Xiaoli Zhang, Xian-Ping Dong
1Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 3089 Kraus Natural Science Building, 830 North University Avenue, Ann Arbor, MI 48109, USA.
Cell
|October 16, 2012
まとめ
哺乳類の二孔チャネル (TPC) は,ナトリウム選択性であり,カルシウム選択性ではなく,NAADPではなくPI(3,5) P(2) によって活性化されます. この発見は,エンドリゾソーム機能とイオン輸送の調節におけるTPCの役割を再定義するものである.
科学分野:
- 細胞生物学 細胞生物学
- イオンチャンネル生理学 イオンチャンネル生理学
- 分子神経科学は分子神経科学である.
背景:
- 哺乳類の二孔チャネルタンパク質 (TPC1,TPCN1,TPC2,TPCN2) は,エンドソームとリソソームに位置しています.
- 以前は,ニコチン酸アデニンジヌクレオチドリン酸塩酸 (NAADP) によって引き起こされるカルシウム放出を媒介すると考えられていた.
研究 の 目的:
- 哺乳類の2孔チャンネル (TPC) のイオン選択性とゲートメカニズムを直接調査する.
- エンドリゾソームで輸送されるプライマリイオンと,臓器細胞機能におけるTPCの役割を明らかにする.
主な方法:
- エンドリゾソーム内のTPCの直接電気生理学的記録.
- 実験では,ワイルドタイプとTPCのダブルノックアウトマウスモデルを使用しました.
主要な成果:
- TPCは,カルシウム選択的ではなく,ナトリウム選択的チャネルであることが判明しました.
- TPCの活性化は,PI{3,5) P{2}に依存し,NAADPから独立していた.
- ナトリウム (Na+) は,エンドリゾソームの主要なイオンとして特定され,カリウム (K+) の支配的な仮定に異議を唱えました.
結論:
- 哺乳類のTPCは,PI ((3,5) P ((2)) によって調節されるナトリウム選択的経路として機能する.
- これらの発見は,エンドリソソームのイオン輸送と膜ポテンシャル調節に関する私たちの理解を修正します.
- この結果は,臓器核融合におけるPI{3,5) P{2}の役割を理解するための新しい基礎を提供します.
関連する概念動画
01:42Phosphoinositides and PIPs
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.
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01:34ATP Driven Pumps II: P-type Pumps
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A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
01:11IP3/DAG Signaling Pathway
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 produces two-second...
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01:28Reabsorption and Secretion in the PCT
The Proximal Convoluted Tubule, or PCT, plays a pivotal role in the body's filtration system. They are primarily responsible for reabsorbing solutes and water from the filtered fluid produced by the glomeruli. Most of the filtered water, ions, and organic solutes such as glucose and amino acids are reabsorbed by the PCT.
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A key example is the...
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A key example is the...
01:27Transducer Mechanism: Enzyme-Linked Receptors
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Major types that are helpful drug targets include:
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