ドロソフィラの孤児核受容体DHR38は,非典型のエクディステロイドシグナル伝達経路を媒介する
Keith D Baker1, Lisa M Shewchuk, Tatiana Kozlova
1Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Cell
|June 18, 2003
まとめ
科学者たちは,既知のエクディステロイド受容体 (EcR) から独立して,DHR38とUSPを含むフルーツハエの新しいホルモンシグナル伝達経路を発見しました. この発見は,種間で保存されている独特の核受容体類を明らかにしています.
科学分野:
- 分子生物学は分子生物学である.
- 発達生物学 発達生物学について
- エンドクリノロジー エンドクリノロジー
背景:
- エクディステロイドは,ドロソフィラの発達を調節する重要なホルモンです.
- エクディステロイド受容体 (EcR) /超スピラクル (USP) 複合体は,エクディステロイド信号伝達の主要な媒介体である.
- すべてのエクディステロイド反応の正確なメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- ドロソフィラの代替エクディステロイドシグナル伝達経路を調査する.
- 発達における移行を媒介するDHR38の役割を特徴づける.
- 核受容体シグナル伝達におけるDHR38の構造的および機能的特性を解明する.
主な方法:
- DHR38-USP複合体の形成を研究するヘテロディメリゼーションアッセイ.
- エクディステロイド反応の独立性を評価するための生化学的分析.
- X線結晶撮影により,DHR38.8の構造を決定する.
主要な成果:
- DHR38はUSPとヘテロディメア複合体を形成し,独特のエクディステロイド信号伝達経路を媒介する.
- このDHR38-USP経路は,EcR受容体とは独立して機能する.
- DHR38には正規のリンガンド結合ポケットがないため,新しい作用メカニズムが示唆されています.
- 構造分析により,DHR38は核受容体の別々の構造クラスであることを明らかにした.
結論:
- DHR38とUSPによって媒介される新しいエクディステロイドシグナル伝達経路は,ドロソフィラに存在する.
- この経路は,EcRとは独立して動作し,DHR38やUSPへの直接的なエクディステロイド結合を伴わない.
- DHR38は,ヒトの保存されたシグナル伝達機構に意味を持つ,構造的に異なる核受容体クラスを表しています.
関連する概念動画
Nuclear Export
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Export of Misfolded Proteins out of the ER
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
Cell Signaling in Plants
Plant cells communicate to coordinate their cycle of growth, flowering and fruiting, and activities in roots, shoots, and leaves in response to the changing environmental conditions. Plant signaling is distinct from animal signaling. Plants primarily utilize enzyme-linked receptors, whereas the largest class of cell-surface receptors in animals are G-protein coupled receptors (GPCRs). Unlike animals, receptor tyrosine kinases are rare in plants. Instead, plants have a diverse class of...
Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...


