概括
质疑了雌激素激素作用的标准模型. 不被占用的雌激素受体主要位于完整细胞的核中,而不是细胞质中.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 已建立的模型假定雌激素受体 (ERs) 位于细胞质中,在结合雌激素时转移到核中.
- 这种模型主要基于使用同质化的细胞制剂的研究,这可能会引入文物.
- 新出现的证据表明,空置的ER可能是核的,细胞质局部化是提取的工件.
研究的目的:
- 为了研究完整细胞中未被占领的雌激素受体的亚细胞局部.
- 挑战关于ER分布的类固醇激素作用的主流模式.
主要方法:
- 利用细胞素B诱导的核化来从GH3细胞中分离细胞质和核质分离物 (来自大鼠垂体瘤).
- 在这些孤立的细胞小部分中量化了雌激素结合活性.
主要成果:
- 细胞质部分表现出极少的雌激素结合活性.
- 大多数未被占用的雌激素受体被发现与核部分 (核细胞) 有关.
结论:
- 雌激素激素作用的标准模型,即将未被占用的ER置于细胞质中,可能是不正确的.
- 不被占用的雌激素受体主要是完整的GH3细胞中的核.
相关概念视频
Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Nuclear Localization Signals and Import
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
Nuclear Export
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
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...
Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:


