赛纳普托塔格明-1将分泌囊泡与合成素-1/SNAP-25受体复合体联系起来
Heidi de Wit1, Alexander M Walter, Ira Milosevic
1Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam and VU Medical Center, 1081 HV Amsterdam, the Netherlands.
Cell
|September 1, 2009
概括
研究人员确定了synaptotagmin-1和SNAP-25作为分泌囊泡对接中的关键蛋白质. 这一发现澄清了外细胞分裂的初始步骤以及Munc18-1在SNARE复合体形成中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
- 生物化学 生物化学
背景情况:
- 分泌囊泡在等离子体膜上对接是一个关键的步骤,在外细胞形成过程中之前的膜融合.
- 囊泡对接蛋白的分子身份及其与SNARE复合组件的连接仍然难以捉摸.
- 了解这些初始对接事件对于破译受调节的外细胞形成的机制至关重要.
研究的目的:
- 为了确定负责分泌囊泡对接的分子成分.
- 阐明特定蛋白质在对接过程中的作用,包括synaptotagmin-1和SNAP-25.
- 为了澄清Munc18-1在对接与膜融合中的功能.
主要方法:
- 在实验研究中利用了上腺胺细胞.
- 采用了诸如交叉救援实验和双击模式等技术.
- 进行了电生理学记录,以评估膜融合动态.
主要成果:
- 确定了synaptotagmin-1作为囊泡对接伙伴和SNAP-25作为血对接因子.
- 确定了synaptotagmin-1,SNAP-25,Munc18-1,和syntaxin构成了最小的对接机制.
- 证明了Munc18-1在对接中的要求可以通过稳定syntaxin/SNAP-25复合体来绕过.
结论:
- 提出一个模型,其中囊泡对接是通过同聚胺-1与合成素/SNAP-25受体复合体结合而发生的.
- 得出结论,Munc18-1对于下游突触基因组合形成融合性SNARE复合体至关重要,而不是对接本身.
- 这些发现为外细胞分裂和SNARE复合体形成的初始阶段提供了分子框架.
相关概念视频
Overview of Secretory Vesicles
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...
Fusion of Secretory Vesicles with the Plasma Membrane
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...
Pinching-off of Coated Vesicles
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...
SNAREs and Membrane Fusion
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...
Vesicular Tubular Clusters
After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
With the help of motor proteins such...
Clathrin Coated Vesicles
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...


