在SNARE组合伴侣Munc13-1中,依赖于二甲基甘油的六合素合作地结合囊泡
Feng Li1,2, Kirill Grushin1,2, Jeff Coleman1,2
1Department of Cell Biology, School of Medicine, Yale University, New Haven, CT 06520.
概括
Munc13-1 蛋白质在脂质双层上形成六合体,对于突触囊泡对接和融合至关重要. 这些Munc13-1六聚合物独立捕获囊泡,澄清了它们在神经传递中的作用.
科学领域:
- 分子生物学分子生物学
- 神经科学是一个神经科学.
- 生物物理学的生物物理.
背景情况:
- Munc13-1对于突触囊泡对接和活跃区域的融合至关重要.
- 了解Munc13-1的寡合体状态和功能是突触传播的关键.
- 富含甲基甘油的微域涉及调节突触蛋白质组合.
研究的目的:
- 为了研究Munc13-1在脂双层上的分子的自我组装.
- 为了确定这些微域内Munc13-1的寡合状态.
- 为了阐明Munc13-1寡合体在囊泡捕获中的功能意义.
主要方法:
- 对Munc13-1集群分布进行系统的Poisson分析.
- 在脂质双层上Munc13-1自我组装的生物物理特征.
- 对影响Munc13-1六合体稳定性和功能的突变进行分析.
主要成果:
- 在脂双层上,Munc13-1自组装成富含二甲基甘油的微域.
- 普森分析表明存在单体和主要的六体Munc13-1寡合体.
- 已识别的六合体具有功能能力,每个都能够独立捕获囊泡.
- 突变破坏六合体接触改变囊泡结合从合作性到渐进性.
结论:
- Munc13-1主要在脂质双层上形成六合体,与单体不同.
- 这些Munc13-1六合体是囊泡捕获的关键功能单元.
- 这些发现澄清了Munc13-1在突触囊泡原始化中的分子机制.
相关概念视频
SNAREs and Membrane Fusion
10.9K
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
10.9K
Pinching-off of Coated Vesicles
3.2K
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...
3.2K
Clathrin Coated Vesicles
7.0K
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...
7.0K
Coat Assembly and GTPases
3.5K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.5K
Fusion of Secretory Vesicles with the Plasma Membrane
11.1K
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
11.1K
Intralumenal Vesicles and Multivesicular Bodies
3.5K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.5K


