酶脚手架Cab39是必要的酸酶敏感NCC的酸激活
Mohammed Z Ferdaus1, Rainelli B Koumangoye1, Paul A Welling2
1Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN (M.Z.F, R.B.K., E.D.).
Hypertension (Dallas, Tex. : 1979)
|January 23, 2024
概括
结合蛋白39 (Cab39) 和类似Cab39的蛋白 (Cab39l) 对于合运输体 (NCC) 在中激活至关重要. 它们的缺失导致一种类似于吉特曼综合征的表型,通过防止SPAK激酶局部化到顶膜.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 调节WNK-SPAK信号通路,这对于激活-平衡的远端卷状管道中的NCC至关重要.
- 结合蛋白39 (Cab39) 和其同类Cab39-like (Cab39l) 假定是SPAK/OSR1激活所必需的,但它们的功能是未知的.
研究的目的:
- 研究Cab39和Cab39l在脏中调节WNK-SPAK/OSR1-NCC通路中的作用.
- 确定Cab39和Cab39l缺乏对NCC功能和SPAK/OSR1局部化的影响.
主要方法:
- 使用可诱导他莫西芬的NCC驱动的淘汰策略生成的Cab39缺乏的小鼠与全球Cab39l淘汰小鼠交叉.
- 通过Western blot分析了蛋白质表达和酸化,测量了血液和尿液的电解质,并进行了针对SPAK和OSR1定位的免疫光学.
主要成果:
- 在远端卷状管中缺少Cab39和Cab39l,导致NCC酸化完全缺失.
- 缺乏Cab39的小鼠显示NCC功能受损,模仿吉特曼综合征.
- SPAK和OSR1未能与顶膜上的NCC同位,而是形成细胞内点.
结论:
- Cab39蛋白对于NCC酸化和正常功能是不可或缺的,因为它们的缺失导致了类似Gitelman的表型.
- 对于SPAK与NCC的适当的顶端膜局部化,Cab39蛋白质是必需的,类似于其酵母同类的功能.
相关概念视频
01:22Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
01:16Calmodulin-dependent Signaling
5.1K
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,...
5.1K
01:27Transducer Mechanism: Enzyme-Linked Receptors
2.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
2.5K
01:30Assembly of Signaling Complexes
5.8K
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,...
5.8K
01:07MAPK Signaling Cascades
5.5K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.5K
00:50Anaphase Promoting Complex
2.9K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K