ベータアレスティン2とGRK2によって媒介される滑らかな物質の活動依存的内部化
Wei Chen1, Xiu-Rong Ren, Christopher D Nelson
1Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. w.chen@duke.edu
まとめ
ソニック・ヘッジホッグ (Shh) 経路のシグナリングには,スムージング (Smo) アクティベーションが含まれています. Gタンパク質結合受容体キナーゼ2 (GRK2) とベータアレスティン2は,脊椎動物の発達に不可欠なSmo内細胞化を媒介する.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 発達生物学 発達生物学について
背景:
- ソニック・ヘッジホッグ (Shh) 信号は脊椎動物の発達に不可欠です.
- パッチド (Ptc) は通常,スムージド (Smo) を抑制し,重要なトランスメブラン受容体である.
- スモアクティベーションとダウンストリームシグナリング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:
- 経路の活性化中にSmoと相互作用する分子を識別する.
- Smoの調節とシグナル伝達におけるこれらの相互作用する分子の役割を解明する.
- GRK2とβ-アレスティン2がSmoの取引と機能に関与するかを調査する.
主な方法:
- 同免疫プレシピテーションアッセイは,SMOとタンパク質の相互作用を検出する.
- 光顕微鏡でタンパク質の局所化と内細胞化を視覚化します.
- 経路の活性を調節するために,Shh,Smoアゴニスト,Smoアンタゴニスト (サイクロパミン) による治療.
主要な成果:
- Gタンパク質結合受容体キナーゼ2 (GRK2) は,活性化時にSmoをリン酸化する.
- ベータアレスティン2は,Smoと活性化依存の形で相互作用する.
- GRK2とβ-アレスティン2は,クラスリンで覆われた穴を通したSmo内分細胞化を促進し,Ptcによって抑制されShhによって緩和されるプロセスである.
結論:
- GRK2とβ-アレスティン2は,活性化されたSMOの新たな相互作用パートナーとして特定されています.
- これらのタンパク質はSmoのエンドサイトーシスを媒介し,信号の終結または調節における役割を示唆しています.
- GRK2とβ-アレスティン2は,ソニック・ヘッジホッグ (Shh) 信号伝達経路における潜在的な重要なメディエーターである.
関連する概念動画
Cell Motility through Blebbing
Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Blebbing Through the Matrix
In multicellular...
Assembly of Signaling Complexes
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,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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...
GPCR Desensitization
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...
IP3/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...


