里林受体ApoER2是适应蛋白复合体AP-4的载荷:对遗传性性的影响
Mario O Caracci1, Héctor Pizarro1, Carlos Alarcón-Godoy1
1Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago, Chile.
Progress in neurobiology
|January 28, 2024
概括
适应蛋白复合体4 (AP-4) 缺乏会损害对Reelin信号传递至关重要的受体ApoER2的流通. 这一发现将AP-4突变与遗传性性 (HSP) 病变发生联系起来.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 适应蛋白复合体4 (AP-4) 对于从跨戈尔吉网络出口蛋白质至关重要.
- 在AP-4子单元的突变导致遗传性性 (HSP),神经疾病.
- 里林信号通路在神经元发育和功能中起着至关重要的作用.
研究的目的:
- 研究AP-4在Reelin通路中的受体ApoER2的贩运中的作用.
- 为了确定ApoER2和AP-4之间的特定相互作用动机.
- 阐明AP-4缺乏对瑞林信号传递和神经元功能的影响.
主要方法:
- 使用了AP4E1-Knockout (KO) HeLa细胞和Ap4e1-KO小鼠海马神经元.
- 采用免疫光显微镜来评估ApoER2与戈尔吉标记物的同定位.
- 分析了KO与野生类型神经元中的ApoER2蛋白表达和生物合成运输.
- 研究了Reelin信号通路激活 (AKT,ERK,CREB) 和KO神经元中的树状树木化.
主要成果:
- 在ApoER2的细胞质域中确定了一种ISSF/Y基因,该基因负责AP-4结合.
- AP-4缺乏导致ApoER2与戈尔吉标记物的同局部化增加,蛋白质表达减少.
- AP-4缺陷改变了ApoER2的戈尔吉后贩运,减少了轴突分布.
- 缺乏AP-4会降低Reelin诱导的ERK酸化,CREB激活和Golgi部署,对AKT和树突树木化有轻微影响.
结论:
- ApoER2是AP-4综合体的一个新型货物,由ISSF/Y主题介绍.
- AP-4对于适当的ApoER2贩运和定位至关重要,特别是在轴突中.
- 缺陷的ApoER2贩运和AP-4缺陷神经元中的改变的Reelin信号可能会导致HSP的发病.
相关概念视频
ER Retrieval Pathway
3.8K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.8K
Directing Proteins to the Rough Endoplasmic Reticulum
7.3K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
7.3K
Receptor-mediated Endocytosis
104.5K
Overview
104.5K
Coat Assembly and GTPases
3.5K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.5K
Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K
Enzyme-linked Receptors
78.4K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
78.4K


