RILP通过抑制内分泌网膜-内分泌细胞相互作用来诱导胆固醇在溶解体中的积累
Yang Han1, Xiaoqing Liu1, Liju Xu1
1State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen 361102, China.
Cells
|August 28, 2024
概括
拉布7交互性溶解体蛋白 (RILP) 抑制了内分泌网膜 (ER) 溶解体接触,破坏了胆固醇的运输,并触发了自. 这项研究阐明了RILP在有机细胞通信和细胞平衡中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 机体生物学 机体生物学
背景情况:
- 细胞内网 (ER) 和内酶体相互作用对于细胞胆固醇恒温至关重要.
- 囊泡关联膜蛋白关联蛋白-OSBP相关蛋白1L (VAP-ORP1L) 相互作用介导ER-lysosome膜接触,由Rab7.7调节.
- 在ER-溶酶体相互作用中,Rab7相互作用溶酶体蛋白 (RILP) 的确切作用尚不清楚.
研究的目的:
- 为了研究RILP在ER-lysosome相互作用和胆固醇运输中的作用.
- 阐明RILP影响器官接触部位的机制.
- 确定RILP介导的干扰对ER-内分泌体通信的下游后果.
主要方法:
- 免疫光显微镜可视化器官的定位和接触点.
- 蛋白相互作用研究,以评估RILP对VAP-ORP1L复合体形成的影响.
- 在RILP操纵后,在内分泌体中分析胆固醇水平.
- 自试验评估细胞对改变胆固醇运输的反应.
主要成果:
- RILP与ORP1L直接相互作用,竞争性地抑制了VAP-ORP1L接触点的形成.
- RILP表达导致晚期内分泌体/溶解体的聚合,减少了ER-内分泌体的接近性.
- 过度表达RILP会导致胆固醇在内溶酶体中的积累,并诱导RILP依赖的自.
结论:
- 通过抑制VAP-ORP1L接触,RILP破坏了ER-内分泌体相互作用.
- 这种干扰会损害从内分泌体到急诊室的胆固醇流动.
- 累积的内溶性胆固醇会触发一个反循环,激活细胞自.
关键词:
在RILP中,RILP是指RILP.拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉布拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉拉自自是自的过程.胆固醇的运输 胆固醇的运输器官相互作用的相互作用.
相关概念视频
01:39Receptor-mediated Endocytosis
104.2K
Overview
104.2K
01:28Assembly of the Lipid Bilayer in the ER
3.1K
Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
3.1K
01:45Regulation of Nuclear Protein Sorting
2.4K
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...
2.4K
01:34Directing Proteins to the Rough Endoplasmic Reticulum
7.2K
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...
7.2K
01:28The Early Endosome: Endocytosis of Transferrin
3.2K
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...
3.2K
01:21Smooth Endoplasmic Reticulum
5.7K
Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
5.7K