透AMPA受体的突触活性诱导受体亚型中的切换
1Department of Pharmacology, University College London, UK.
Nature
|June 6, 2000
概括
突触活动迅速改变大脑星状细胞中的α-amino-3-hydroxy-5-methyl-4-isoxazole酸受体 (AMPAR) 组成. 这种变化通过结合含有GluR2的AMPARs来改变突触传输,调节的透性.
科学领域:
- 神经科学是一个神经科学.
- 突触性可塑性 突触性可塑性
- 分子生物学分子生物学
背景情况:
- 活动依赖的突触可塑性对中枢神经系统的功能至关重要.
- 后突触修饰通常涉及α-amino-3-hydroxy-5-methyl-4-isoxazole酸受体 (AMPAR) 响应性的变化.
- 现有的模型表明AMPAR数和酸化状态的变化驱动了这些变化.
研究的目的:
- 研究一种新型的突触可塑性,涉及AMPAR亚单元组成和Ca2+透性.
- 阐明GluR2亚单元在小脑星状细胞突触中的活动依赖性突触修饰中的作用.
主要方法:
- 利用电生理学技术来监测突触电流.
- 研究了AMPARs的Ca2+透性和聚胺阻断.
- 在突触刺激后跟踪了含有GluR2的AMPARs的结合.
主要成果:
- 确定了AMPAR亚单元组成和大脑星状细胞突触中的Ca2+透性的快速,持久的变化.
- 证明了Ca2+透性AMPARs的重复突触激活导致Ca2+透性降低.
- 表明通过缺乏GluR2的AMPARs产生的活性诱导的Ca2+流入调节了含有GluR2的AMPARs的向.
结论:
- 通过缺乏GluR2的AMPARs,依赖活动的Ca2+流入控制了含有GluR2的AMPARs的结合.
- 这一过程代表了突触传输效率的自我调节机制.
- 突出了一种新型的突触可塑性,这种可塑性是由AMPAR亚单元组成的变化介导的.
相关概念视频
Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Membrane Asymmetry Regulating Transporters
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Adrenergic Receptors: ɑ Subtype
Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...


