在synaptobrevin/VAMP淘汰赛小鼠中分析了SNARE功能
S Schoch1, F Deák, A Königstorfer
1Center for Basic Neuroscience, Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
概括
可溶性NSF附着蛋白受体 (SNAREs) 是膜融合的关键. 这项研究表明,synaptobrevin 2对于快速触发的聚变至关重要,但对于所有突触囊泡聚变事件来说并不必不可少.
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
- 分子生物学分子生物学
背景情况:
- 可溶性NSF附着蛋白受体 (SNAREs) 对于膜融合至关重要.
- 在聚变特异性,催化或执行中SNARE的确切作用仍在争论中.
- 突触组维因/VAMP 2 是前脑中突触囊泡融合的关键SNARE蛋白.
研究的目的:
- 为了研究synaptobrevin 2在突触囊泡融合中的精确功能.
- 区分SNARE在聚变特异性,催化或执行方面的拟议作用.
主要方法:
- 产生缺少 synaptobrevin/VAMP 的淘汰小鼠 2.
- 电生理学记录以测量突触囊泡融合速率.
- 评估自发的,高压的糖糖诱导和Ca2+触发的融合.
主要成果:
- 突触囊泡融合,无论是自发的还是高压的糖糖诱导,在 synaptobrevin 2 淘汰赛小鼠中减少了 ~ 10 倍.
- 快速Ca2+触发的突触囊泡融合在没有Synaptobrevin 2的情况下减少了100倍以上.
- 这些发现表明,synaptobrevin 2对于快速,依赖的融合至关重要.
结论:
- Synaptobrevin 2 在催化聚变反应和稳定聚变中间体方面发挥着重要作用.
- 虽然对于高效的突触囊泡融合至关重要,但对于所有融合事件来说,synaptobrevin 2并不绝对是必需的.
- 数据表明,在一个模型中,synaptobrevin 2对于快速,调节的聚变至关重要,但对于基底或非特异性聚变过程却不重要.
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...
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...
Receptor Downregulation in MVBs
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 activation may...
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Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.


