血清蛋白转化酶亚素/素9型和细胞表面低密度脂蛋白受体:证据表明相互调节
Hagai Tavori1, Daping Fan, John L Blakemore
1Vanderbilt University, Cardiovascular Medicine, Nashville, TN 37232-6300, USA.
Circulation
|May 22, 2013
概括
低密度脂蛋白 (LDL) 受体 (LDLR) 是清除9型 (PCSK9) 蛋白转化酶亚素/素的主要途径. 这种LDLR和PCSK9之间的相互调节控制胆固醇水平.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 心血管科学 心血管科学
背景情况:
- 蛋白转化酶亚素/素9型 (PCSK9) 调节低密度脂蛋白受体 (LDLR) 降解,影响血清胆固醇.
- 缺陷的LDLR会导致高胆固醇血清,但不会影响PCSK9的清除.
研究的目的:
- 为了研究PCSK9和LDLR之间的相互相互作用.
- 为了确定它们对血清胆固醇水平的综合作用.
主要方法:
- 产生表达人类PCSK9.9的转基因小鼠.
- 在各种组织 (肝脏,脏,上腺) 中分析LDLR降解.
- 测量野生型,LDLR ((-/-) 和LDLR ((+/-) 类小鼠的血清PCSK9和胆固醇水平.
主要成果:
- 人类PCSK9主要导致肝脏中的LDLR降解,尽管脏表达.
- PCSK9增加了独立于LDLR的脂蛋白的肝脏分泌.
- PCSK9表达提高了血清PCSK9水平,而LDLR表达则降低了它们.
- 在存在功能性LDLR的情况下,PCSK9清除显着更快.
结论:
- LDLR是PCSK9消除的主要途径.
- 在LDLR和PCSK9.9之间存在相互调节关系.
- 这种相互作用控制了血清PCSK9,肝脏LDLR表达,并最终控制了血清LDL水平.
相关概念视频
Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Receptor-mediated Endocytosis
Overview
Receptor-mediated Endocytosis
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
Transducer Mechanism: Enzyme-Linked Receptors
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:
Cholesterol: Significance and Regulation
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...


