通过破坏SNARE复杂组件,APOE4触发了失调的突触囊释放,从而触发了SNARE复杂组件的释放
Feng Chen1,2,3, Yanting Chen1, Sifan Feng1
1Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, China.
Cellular and molecular life sciences : CMLS
|June 23, 2025
概括
阿波利波蛋白E4 (APOE4) 蛋白质通过阻断可溶性N-乙烯胺胺敏感因子附着蛋白受体 (SNARE) 复合体的组合,从而影响神经疾病风险,从而损害了突触传输.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 阿波利波蛋白E (APOE) ε4等位基因是神经退行性疾病的重要遗传风险因素.
- 在这些条件下,受损的突触传输是常见的病理特征.
研究的目的:
- 阐明将APOE ε4与神经退行症联系起来的致病机制.
- 研究APOE与突触囊泡释放机制之间的相互作用.
主要方法:
- 蛋白质组学分析
- 同免疫沉 (Co-IP) 是一种共免疫沉.
- 双分子光补充 (BiFC) 试验法
- 在体外和体内研究.
主要成果:
- APOE与VAMP2相互作用,这是SNARE复合体的关键组成部分,与APOE3.3相比,APOE4变体的亲和力更高.
- APOE4 抑制了 SNARE 复合体的组合,可能通过液态-液态相分离 (LLPS).
- 这种抑制会负面调节突触囊泡的释放.
结论:
- 通过阻碍SNARE复合体的形成,APOE4破坏了突触囊泡的释放.
- 这种机制为APOE在神经退行性疾病的发病过程中的作用提供了洞察力.
- 这些发现为开发针对APOE的神经疾病的治疗提供了理论基础.
相关概念视频
Fusion of Secretory Vesicles with the Plasma Membrane
12.0K
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...
12.0K
SNAREs and Membrane Fusion
11.1K
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...
11.1K
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
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
Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
461
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
461
Chemical Synapses
9.2K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
9.2K


