Gα子单位的Gq/11家族对于下发育是必要的,也是足够的
Stanley M Kanai1, Chloe R Garcia1, MaCalia R Augustus1
1Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO USA.
bioRxiv : the preprint server for biology
|September 30, 2024
概括
Gq/11蛋白对于斑马鱼的下巴发育至关重要,它调解来自Endothelin受体A型 (Ednra) 的信号. 激活Gq/11可以恢复形状,甚至可以将上结构转化为下形状.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 脊椎动物的部发育依赖于保存的信号通路,包括内分泌素1 (Edn1) 和内分泌素受体A型 (Ednra).
- 精确的细胞内机制连接EDNRA激活到模式的基因调节还没有完全理解.
- Gq/11家族的Gα子单元涉及到各种细胞信号通路.
研究的目的:
- 调查Gq/11 Gα子单元在斑马鱼下发育过程中调解Ednra信号传递中的作用.
- 为了确定Gq/11活动是否对于依赖Ednra的下模式是必要和足够的.
主要方法:
- 使用斑马鱼作为模型生物.
- 采用药理抑制和基因切除来降低Gq/11活动.
- 使用转基因方法在胚胎中诱导具有Endothelin 1 (edn1) 突变的构成性活性Gq蛋白.
- 分析了下巴结构的发展和基因表达模式.
主要成果:
- 在EDN1突变胚胎中观察到的发育缺陷中,Gq/11活动的遗传损失是复制的,G11基因尤其重要.
- 恢复edn1突变胚胎中的Gq活性,挽救了Edn1/Ednra依赖的部结构和基因表达特征.
- 实验性诱导Gq活动导致了同源性,将上结构转化为像下结构.
结论:
- Gq/11 Gα子单元是斑马鱼下模式中Ednra信号的重要媒介.
- Gq/11活动是既必要又足够的,以建立下的身份下游的Ednra.
- 这些发现为控制面发育的细胞内信号级联提供了关键的见解.
相关概念视频
Activation and Inactivation of G Proteins
6.8K
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...
6.8K
Small GTPases - Ras and Rho
3.9K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
3.9K
GTPases and their Regulation
8.3K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
8.3K
Transducer Mechanism: G Protein–Coupled Receptors
1.9K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
1.9K
G Protein-coupled Receptors
11.5K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
11.5K
Determination
18.2K
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
18.2K


