EphB2受体的配体偏好是通过N-糖化酶选择性调节的
Chunyu Lyu1, Lin Yuan2, Yang Yang1
1Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China.
iScience
|May 7, 2025
概括
埃弗林-B2特别激活神经元中的EphB2受体,与埃弗林-A5.5不同. 在EphB2上的N-糖化位点对于这种选择性结合和下游信号传递至关重要,影响神经元发育.
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
- 细胞生物学 细胞生物学
背景情况:
- 埃弗受体和埃弗林配体是细胞通信和神经元发育的关键媒介.
- 埃弗 / 埃弗林相互作用是复杂的,对于正常的神经系统功能至关重要.
研究的目的:
- 研究EphB2受体对以弗林配体的特定结合偏好背后的分子机制.
- 确定EphB2ectodomain和N-glycosylation在以弗林结合选择性和下游信号传导中的作用.
主要方法:
- 在EphB2受体上利用域交换和N/Q突变发生.
- 使用以林-B2和以林-A5.5研究的结合特异性.
- 分析了N-糖化位的进化保护.
- 在初级皮层神经元中评估了对细胞圆和树突脊柱形成的功能影响.
主要成果:
- 埃弗林-B2,而不是埃弗林-A5,在初级皮层神经元中专门识别和激活EphB2.
- 埃弗B2的ectodomain和特定的N-糖化位点 (N265,N336,N428,N482) 对于选择性以弗林结合至关重要.
- 这些部位的突变使得EphB2无法区分以弗林-B2和以弗林-A5.
- 在Eph家族成员中保持N-糖化,对于EphB2信号传递至关重要,包括细胞圆和树突脊柱形成.
结论:
- EphB2的N-糖化决定了它与以弗林-B2的特定结合,为Eph/ephrin相互作用的特异性提供了分子基础.
- 这种以N-甘氨酸为导向的结合机制被保存,在神经元发育和信号通路中起着至关重要的作用.
相关概念视频
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
Receptor Downregulation in MVBs
2.0K
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...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
Oligosaccharide Assembly
2.7K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.7K
Ligand Binding Sites
12.6K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.6K
Selectins
3.2K
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
3.2K
Amplifying Signals via Enzymatic Cascade
8.2K
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...
8.2K


