血清蛋白酶TMPRSS6是需要感知缺铁的
Xin Du1, Ellen She, Terri Gelbart
1Department of Genetics, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
概括
研究人员确定了一种基因缺陷,导致小鼠缺铁性贫血和脱发. 这种缺陷导致高水平的肝素,阻断铁的吸收,影响身体的铁调节.
科学领域:
- 生物化学 生物化学
- 遗传学 是一个遗传学.
- 身体生理学 身体生理学
背景情况:
- 肝素是身体铁含量的关键调节剂,控制肠道铁的吸收.
- 在铁耗竭期间抑制肝素基因 (Hamp) 表达的机制尚不清楚.
研究的目的:
- 为了研究铁缺乏期间的Hamp抑制背后的分子机制.
- 为了确定参与调节肝素表达和铁平衡的遗传因素.
主要方法:
- 一种新型老鼠突变表型的表征,称为"面具",表现出脱发和微细胞贫血.
- 基因分析以确定引起的基因缺陷.
- 涉及基因和蛋白质过度表达的功能研究,以阐明TMPRSS6在Hamp调节中的作用.
主要成果:
- "面具"表型是由于跨膜血清蛋白酶6基因 (Tmprss6) 的拼接缺陷引起的.
- 这种缺陷导致高水平的肝素,导致饮食中的铁吸收减少和贫血.
- 正常的TMPRSS6蛋白的过度表达抑制了Hamp促进体的激活,这表明它在阻断肝素转录中的作用.
结论:
- TMPRSS6对于检测缺铁和抑制肝素转录至关重要.
- 这一途径允许在体内缺铁时增加食铁的吸收.
- TMPRSS6 作为维持铁平衡的重要组成部分.
相关概念视频
The Early Endosome: Endocytosis of Transferrin
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Riboswitches
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
Microbes and Other Elemental Cycles
Microbial activity plays a pivotal role in the biogeochemical cycling of iron and manganese, especially at the redox gradients characteristic of stratified aquatic environments. These cycles are driven by microbial transformations between oxidized and reduced forms of the metals, allowing organisms to exploit them for metabolic energy and structural purposes.Iron Cycling Across Redox GradientsIn neutral, oxygen-rich surface waters, iron is predominantly found in its oxidized, insoluble ferric...

