人类寡头细胞的原生细胞通过TAM受体激活来调解突触消除
Asimenia Gkogka1, Susmita Malwade1, Marja Koskuvi1
1Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Nature communications
|December 5, 2025
概括
寡头细胞原生细胞 (OPCs) 在人类大脑中内化突触物质. 这个过程是由GAS6-AXL信号驱动的,这揭示了OPC在人类发育过程中在突触重塑中的新角色.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 众所周知,寡头细胞原生细胞 (OPCs) 在动物模型中参与突触重塑.
- 人类大脑发育中的OPCs的精确机制和相关性尚未完全理解.
研究的目的:
- 在人类大脑发育模型中,研究OPC与突触材料相互作用和内化的机制.
- 在早期人类大脑发育期间,确定参与OPC-突触相互作用的关键信号通路.
主要方法:
- 人类多系前脑器官模型的生成.
- 单核转录组分析和细胞间通信分析.
- 药物抑制和特定信号通路的基因操纵.
主要成果:
- 人体器官中的OPC与突触形成密切联系,并内化突触材料.
- 特定于增长停止基因6 (GAS6) -TYRO3,AXL和MERTK (TAM) 受体轴被确定为一个关键的信号通路.
- GAS6是由神经元和微质表达的,而AXL是由OPCs的一个子集表达的.
- 抑制TAM受体,特别是AXL,损害了OPCs的突触吸收.
结论:
- 在早期人类大脑发育过程中,GAS6-AXL信号对OPCs的突触物质内化至关重要.
- 这项研究揭示了AXL表达OPC在突触重塑中的新功能.
- 这些发现提供了关于人类神经发育过程中质细胞和突触之间的复杂相互作用的见解.
相关概念视频
Export of Misfolded Proteins out of the ER
5.0K
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...
5.0K
Receptor Downregulation in MVBs
2.7K
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...
2.7K
Neurogenesis and Regeneration of Nervous Tissue
1.5K
In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
1.5K
Enzyme-linked Receptors
85.6K
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...
85.6K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.7K
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...
3.7K


