α2δ表达式设置了前突触通道丰度和释放概率
Michael B Hoppa1, Beatrice Lana, Wojciech Margas
1Department of Biochemistry, Weill Cornell Medical College, New York, New York 10023, USA.
Nature
|June 9, 2012
概括
该研究显示,α2delta (α2δ) 子单元调节突触电压通道 (VGCC) 的水平和功能. 这些子单元通过在突触处实现高效的 (Ca2+) 流入和外细胞形成来提高神经递质释放的概率.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 突触传输是突触传输的过程.
背景情况:
- 突触神经递质的释放取决于 (Ca2+) 通过活跃区域的电压通道 (VGCC) 流入活性区.
- 控制VGCC在突触中的丰度和功能的机制尚未完全理解.
- α2delta (α2δ) 子单元与VGCC相关,是用于神经病痛的 gabapentinoids 的标.
研究的目的:
- 调查α2δ子单元在调节突触VGCC丰度和功能的作用.
- 阐明α2δ子单元调节突触前神经递质释放的分子机制.
主要方法:
- 在老鼠中过度表达毛孔形成的α1(A) VGCC亚单元,以评估其对突触VGCC水平的影响.
- 分析α2δ子单位在调节VGCC丰度和释放概率中的功能.
- 研究金属离子依赖粘附位点 (MIDAS) 图案在α2δ子单元中的作用.
主要成果:
- 单独过度表达α1 (A) 亚单元并没有改变突触VGCC的丰度或功能,这表明了取决于贩运的调节.
- 发现α2δ子单元设置了突触VGCC的丰富性,作为陪伴者.
- 具有完整的MIDAS基因的α2δ子单元显著增加了释放概率 (80%) 并保护了Ca2+化对外细胞形成的可能性,这表明在配置VGCC中发挥了有效的外细胞形成的作用.
结论:
- α2δ子单元在突触功能中扮演着双重角色:它们调节了VGCC向突触的流通,并配置VGCC来增强Ca2+驱动的外细胞形成.
- 在α2δ子单元中的MIDAS图案对于调节释放概率和Ca2+灵敏度至关重要.
- 这些发现凸显了α2δ子单元在突触传输和疼痛调制中的临床重要性.
更多相关视频
12:01Acute Dissociation of Lamprey Reticulospinal Axons to Enable Recording from the Release Face Membrane of Individual Functional Presynaptic Terminals
Published on: October 1, 2014
18:11Quantifying Synapses: an Immunocytochemistry-based Assay to Quantify Synapse Number
Published on: November 16, 2010
相关概念视频
01:16Calmodulin-dependent Signaling
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,...
01:27Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
01:26Chemical Synapses
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...
01:26Chemical Synapses
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...
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
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...