C型ナトリウレチンペプチド (CNP) によってB型ナトリウレチンペプチド受容体の選択的活性化
K J Koller1, D G Lowe, G L Bennett
1Department of Molecular Biology, Genentech, Inc., South San Francisco 94080.
まとめ
C型ナトリウレチンペプチド (CNP) は,心房ナトリウレチンペプチド (ANP) や脳ナトリウレチンペプチド (BNP) とは異なり,ANPR-B受容体を選択的に活性化します. この発見は,ナトリウレチンペプチド受容体シグナル伝達と流体ホメオスタシス調節に関する洞察を提供します.
科学分野:
- エンドクリノロジー エンドクリノロジー
- 分子薬理学 分子薬理学
- 神経内分泌学の神経内分泌学
背景:
- ナトリウレチンペプチドは,血圧と液体バランスを調節するホルモンです.
- 2つの細胞表面受容体ガニリルサイクラゼ,ANPR-AとANPR-Bは,ナトリウレチンペプチドの活動を媒介する.
- アトリアルナトリウレチンペプチド (ANP) と脳ナトリウレチンペプチド (BNP) は主にANPR-Aを活性化します.
研究 の 目的:
- C型ナトリウレチンペプチド (CNP) の特定の受容体相互作用を調査する.
- CNPがANPR-Bを活性化するかどうか,ANPとBNPと比較してその選択性を判断する.
- 中枢神経系の調節におけるCNP-ANPR-B軸の潜在的な役割を調査する.
主な方法:
- 異なるナトリウレチンペプチドによるガニリルサイクラース活性化の評価.
- ANPR-AとANPR-Bを発現する細胞におけるグアノシン3',5'-モノフォスファートの蓄積を測定する.
- ANPR-Bに対するCNP,ANP,BNPの結合親和を比較する.
主要な成果:
- C型ナトリウレチンペプチド (CNP) は,ヒトのANPR-B受容体を強力かつ選択的に活性化します.
- CNPは,ANPR-A.を発現する細胞における周期性GMPを有意に増加させなかった.
- CNPはANPR-Bに対してANPやBNPよりも50~500倍高い親和性を示した.
結論:
- CNPは,ANPR-B受容体の選択的活性化剤である.
- CNP-ANPR-Bシグナル伝達経路は,ナトリウレチンペプチドシステム内の独特なメカニズムを表しています.
- このリンガンド受容体ペアは,中枢神経系の流体恒常の調節に重要な役割を果たす可能性がある.
関連する概念動画
Conservative 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...
RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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...
Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
T Cell Activation and Clonal Selection
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
B Cell Activation and Differentiation
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...


