不同的机制控制神经蛋白1和神经蛋白2的特定突触功能
Jinzhao Wang1,2,3,4, Thomas Sudhof5,6,7, Marius Wernig8,9,10
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
EMBO reports
|January 3, 2025
概括
神经蛋白1和神经蛋白2由于它们的细胞外域而表现出突触特异性. 然而,不同的细胞内机制在激发性与抑制性突触功能中的作用中介.
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
- 突触性可塑性 突触性可塑性
背景情况:
- 神经蛋白是突触后细胞粘附分子,对突触功能至关重要.
- 神经蛋白1 (Nlgn1) 和神经蛋白2 (Nlgn2) 表现出异型特异性,其中Nlgn1在刺激性和Nlgn2在抑制性突触中.
- 这种激发/抑制 (E/I) 特异性的分子基础在很大程度上仍然未知.
研究的目的:
- 阐明Neuroligin 1和Neuroligin 2的E/I突触特异性的基础机制.
- 确定细胞外和细胞内领域在神经蛋白功能和局部化中的作用.
主要方法:
- 野生类型和突变神经蛋白的综合结构功能分析.
- 在缺乏内源性神经蛋白的培养海马神经元中进行功能性救援实验.
- 电生理学评估突触传输恢复.
- 构建和分析仿真Nlgn1-Nlgn2蛋白质.
主要成果:
- Nlgn1和Nlgn2分别选择性地恢复了激发性和抑制性突触传输.
- 细胞外神经蛋白域决定突触特异性,而细胞内序列在很大程度上是可交换的.
- 与Nlgn1.1不同的是,Nlgn2的细胞质序列,包括其结合Gephyrin的基因,对于其功能至关重要.
结论:
- 通过它们的细胞外序列,Nlgn1和Nlgn2都实现了E/I突触特异性.
- 通过Nlgn1和Nlgn2,Nlgn1和Nlgn2使用不同的细胞内机制来促进正常的突触连接.
- 这项研究揭示了尽管保留了细胞外特异性决定因素,但神经蛋白功能的细胞内调节差异.
更多相关视频
11:20Osmotic Avoidance in Caenorhabditis elegans: Synaptic Function of Two Genes, Orthologues of Human NRXN1 and NLGN1, as Candidates for Autism
Published on: December 11, 2009
11.7K
04:47Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System
Published on: May 22, 2020
3.5K
相关概念视频
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.1K
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...
2.1K
03:14Notch Signaling Pathway
4.2K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.2K
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
01:26Chemical Synapses
8.7K
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...
8.7K
01:23Catenins
2.3K
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.3K
01:09Synaptic Signaling
5.5K
Neurons communicate at synapses, or junctions, to excite or inhibit the activity of other neurons or target cells, such as muscles. Synapses may be chemical or electrical.
Most synapses are chemical, meaning an electrical impulse or action potential spurs the release of chemical messengers called neurotransmitters. The neuron sending the signal is called the presynaptic neuron, and the neuron receiving the signal is the postsynaptic neuron.
The presynaptic neuron fires an action potential that...
Most synapses are chemical, meaning an electrical impulse or action potential spurs the release of chemical messengers called neurotransmitters. The neuron sending the signal is called the presynaptic neuron, and the neuron receiving the signal is the postsynaptic neuron.
The presynaptic neuron fires an action potential that...
5.5K