通过PI(3,5) P2和小分子激动剂的TRPML2通道调节控制了内分体囊泡动力学
Zi-Qi Gu1, Hsuan-Ti Wang2, Yanfen Li3
1Laboratory of Host-Microbe Interactions and Cell Dynamics, Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan; Institute of Microbiology and Immunology, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
概括
暂时受体潜在粘脂蛋白-2 (TRPML2) 通道调节囊泡的流通. 小分子激活TRPML2,恢复内体细胞的运动性和纠正缺陷,甚至绕过脂质调节.
科学领域:
- 细胞生物学 细胞生物学
- 离子通道 离子通道
- 膜贩卖 膜贩卖 膜贩卖 膜贩卖
背景情况:
- TRPML2是一个由PI(3,5)P2.2.封闭的内解体通道.
- 它的确切位置和在囊泡贩运中的作用尚未完全理解.
研究的目的:
- 确定TRPML2的亚细胞定位和在囊泡贩运中的功能重要性.
- 研究TRPML2激活和治疗潜力的小分子激动剂.
主要方法:
- 使用Rab4标记物识别TRPML2局部化.
- 对PI{3,5) P2不敏感的TRPML2突变体 (R310A) 的分析.
- 用TRPML2激动剂 (ML2-SA1,ML2-SA2) 进行补丁记录和功能成像.
主要成果:
- TRPML2局限于Rab4阳性循环内分泌体.
- 突变的R310A显示动力受损和周核囊泡积累.
- ML2-SA1和ML2-SA2激活野生类型和突变TRPML2,拯救囊泡贩运缺陷.
- 激动剂恢复功能独立于PI(3,5) P2.2.
结论:
- TRPML2对于Rab4依赖的囊泡贩运是必不可少的.
- 小分子激动剂为TRPML2相关的贩运障碍提供治疗策略.
- TRPML2是一种可用药物的标,用于涉及内体压力和脂质信号缺陷的疾病.
相关概念视频
The Early Endosome: Endocytosis of Transferrin
3.4K
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...
3.4K
Overview of Secretory Vesicles
8.7K
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
8.7K
Phosphoinositides and PIPs
8.7K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.7K
Pinching-off of Coated Vesicles
3.3K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.3K
Receptor Downregulation in MVBs
2.1K
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...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
Clathrin Coated Vesicles
7.3K
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
7.3K


