对于Ca2+道集群和突触囊泡初始化而言,单独的活性区蛋白机械的分子定义
Javier Emperador-Melero1, Jonathan W Andersen1, Sarah R Metzbower2
1Department of Neurobiology, Harvard Medical School, Boston, USA.
bioRxiv : the preprint server for biology
|November 14, 2023
概括
活性区域通过分离通道 (CaV2) 聚合和囊泡原始化机制,精确地组织神经递质释放. 林α和PTPσ蛋白特别组装了独立于CaV2组织的原始化位点.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 突触传输是突触传输的过程.
背景情况:
- 突触处的活性区域通过组织CaV2通道和原始囊泡,确保神经递质的快速释放.
- 一个普遍的模型表明,脚手架蛋白直接将囊泡与CaV2通道连接起来,以获得时间精确度.
- 活跃区域的精确分子结构仍然不完全理解.
研究的目的:
- 为了调查CaV2通道聚类和囊泡原始化机器是否由共享的脚手架蛋白共同组织.
- 阐明在活跃区域的CaV2通道组织和囊泡原始化背后的独特分子机制.
- 为了确定参与组装囊泡启动机械的关键蛋白质.
主要方法:
- 利用海马突触和异质细胞系统进行分子和细胞分析.
- 通过共同免疫沉和成像技术研究了蛋白质的共同定位和复杂的形成.
- 采用了淘汰策略 (Liprin-α1-4) 来评估突触传输中的蛋白质功能.
主要成果:
- 在活性区内,CaV2纳米团和Munc13介导的囊泡原始化站点由单独的机器组织.
- 活跃区域组织者RIM通过不同的相互作用模式将CaV2和Munc13复合体定.
- 素α和PTPσ蛋白与RIM和Munc13一起,独立于CaV2聚类机制,形成了原始化复合体.
结论:
- 活跃区域包括独特的分子复合体,用于组织CaV2通道和囊泡初始化.
- 素α和PTPσ在活性区域组装囊泡启动机械方面发挥着至关重要的作用.
- 这种模块化组织允许精确的时空控制神经递质释放.
相关概念视频
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
Overview of Secretory Vesicles
8.6K
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...
8.6K
Vesicular Tubular Clusters
2.5K
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...
2.5K
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
Calmodulin-dependent Signaling
5.2K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.2K
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


