NAADPは,酸性臓器細胞からカルシウムを2つの毛穴のチャネルを通して動員します
Peter J Calcraft1, Margarida Ruas, Zui Pan
1Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, Scotland, UK.
Nature
|April 24, 2009
まとめ
二孔チャネル (TPC) は,ニコチン酸アデニン・ディヌクレオチド・リン酸塩酸 (NAADP) 受容体として識別されます. これらのTPCは,酸性有機体からカルシウムを放出し,より広範な細胞カルシウムシグナル伝達経路に影響を与えます.
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.
- 生理学 生理学とは
背景:
- 細胞内貯蔵物からカルシウム (Ca2+) を動員することは,細胞シグナル伝達に不可欠です.
- イノシトール-1,4,5-トリフォスファート (InsP3) とサイクルADPリボースは,InsP3RsとRyRs経由でCa2+の放出を調節する.
- NAADPの標的と受容体は議論の余地があるが,ライソソーム関連コンパートメントが関与している.
研究 の 目的:
- NAADP受容体の分子同一性を特定するために.
- NAADP媒介のCa2+シグナル伝達におけるTPCの役割を明らかにする.
- 細胞Ca2+調節に対するTPCの貢献を理解するために.
主な方法:
- HEK293細胞におけるヒトのTPC1,TPC2,鶏のTPC3の発現.
- TPC2濃縮膜に対するNAADP結合親和性の評価.
- ライソソーム性陽子グラデーションの破壊とTPC2アブレーションを含む様々な条件下でNAADP誘発のCa2+放出の調査.
主要な成果:
- TPCs (TPC1,TPC2,TPC3) は,エンドソームおよびリソーム膜に局在しています.
- TPC2は高親和性NAADP結合を示し,ライソソーム関連貯蔵からNAADP誘発のCa2+放出を媒介する.
- NAADP誘発のCa2+放出は,リゾソームの陽子グラデーションとTPC2発現に依存し,InsP3Rs経由でCa2+信号を放大することができる.
結論:
- TPCはNAADP受容体として機能し,酸性有機体からCa2+を放出します.
- このCa2+の放出は,サルコプラズマ/エンドプラズマ網膜を通じた二次信号伝達イベントを開始することができます.
- TPCは,細胞Ca2+シグナリングの調節と組織,NAADPの生理学的役割に関する新しい洞察を提供します.
関連する概念動画
ATP Driven Pumps II: P-type Pumps
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
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...
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...
Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
The ADP/ATP Carrier Protein
ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Movement of Organelles and Vesicles
In eukaryotic cells, cytoskeletal filaments such as actin, microtubules, and intermediate filaments form a mesh-like cytoskeletal network. These filaments serve as tracks for transporting cellular cargo. Specialized motor proteins use the chemical energy stored in adenosine triphosphate (ATP) for this transport. During interphase, microtubules are polarized, with the plus-end towards the cell periphery and the minus-end towards the cell center. Two microtubule-associated motor proteins,...


