通过抑制IGF1R活动,LTK和ALK促进神经元极性和皮质迁移
Tania Christova1, Stephanie Ky Ho1, Ying Liu1
1Department of Biochemistry, Donnelly Centre, University of Toronto, Toronto, ON, Canada.
EMBO reports
|June 9, 2023
概括
受体氨酸激酶Ltk和Alk的损失会破坏神经元的极性和迁移,导致大脑发育和功能异常. 这些发现强调了Ltk和Alk对于建立正确的神经元连接至关重要.
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
- 发展生物学 发展生物学
背景情况:
- 神经元极性对大脑发育和电路形成至关重要.
- 受体氨酸激酶在细胞过程中起着至关重要的作用.
研究的目的:
- 研究受体氨酸激酶Ltk和Alk在神经元极化和迁移中的作用.
- 阐明Ltk和Alk在发育中的大脑中的功能背后的分子机制.
主要方法:
- 使用初级小鼠胚胎神经元进行体外研究.
- 在不同发育阶段 (胚胎,幼,成年人) 检查了Ltk和Alk淘汰赛小鼠模型.
- 分析了细胞表面受体表达,信号通路 (PI3K) 和神经元形态.
主要成果:
- 在发育中的神经元中,Ltk和/或Alk的损失导致了"多个轴突"的表型.
- 缺少Ltk和Alk导致神经元迁移延迟,并破坏皮质模式.
- 在成年人皮层中观察到异常的神经突出的预测和体缺陷.
- Ltk和Alk缺乏增加了细胞表面Igf-1r表达和PI3K信号,驱动了过多的轴突表型.
结论:
- Ltk和Alk是神经元极性和辐射迁移的关键调节者.
- 破坏Ltk和Alk功能会导致大脑发育和组织的重大缺陷.
- 这些发现表明Ltk和Alk是神经系统疾病的潜在治疗点.
相关概念视频
Cell Polarization by Rho Proteins
2.7K
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
2.7K
Enzyme-linked Receptors
78.9K
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...
78.9K
Hedgehog Signaling Pathway
7.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K


