A Role for Frizzled and Their Post-Translational Modifications in the Mammalian Central Nervous System.
A Role for Frizzled and Their Post-Translational Modifications in the Mammalian Central Nervous System.
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DOI：
10.3389/fcell.2021.692888
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发表时间：
2021
影响因子：
5.5
通讯作者：
Salinas PC
中科院分区：
文献类型：
--
作者：
Pascual-Vargas P;Salinas PC
Wnt通路是调节神经元回路的形成和功能的关键信号级联。Wnt的主要受体是Frizzled（Fzd），其介导多种功能，例如神经发生、轴突引导、树突发生、突触形成和突触可塑性。这些过程对于组装从感觉和运动任务到认知表现的各种功能所需的功能性神经元回路至关重要。事实上，异常的Wnt-Fzd信号传导与发育期间和神经退行性疾病如阿尔茨海默病中的突触缺陷有关。新的研究表明，Fzd受体的定位和稳定性在决定Wnt功能方面起着至关重要的作用。Fzd的翻译后修饰（PTMs）正在成为调节这些Wnt受体的重要机制。然而，仅磷酸化和糖基化被描述为调节中枢神经系统（CNS）中的Fzd功能。在这篇综述中，我们讨论了Fzd在神经元回路连接中的功能以及PTM如何促进其功能。我们还讨论了其他PTM，尚未在中枢神经系统中描述，以及它们如何可能调节Fzd在神经元连接中的功能。PTM可以通过影响Fzd在质膜上的定位和稳定性来调节Fzd功能，从而导致Wnt信号传导的局部效应，这是在极化细胞如神经元中特别重要的特征。我们的评论强调了进一步研究PTM对Fzd受体在神经元连接方面的作用的重要性。
The Wnt pathway is a key signalling cascade that regulates the formation and function of neuronal circuits. The main receptors for Wnts are Frizzled (Fzd) that mediate diverse functions such as neurogenesis, axon guidance, dendritogenesis, synapse formation, and synaptic plasticity. These processes are crucial for the assembly of functional neuronal circuits required for diverse functions ranging from sensory and motor tasks to cognitive performance. Indeed, aberrant Wnt–Fzd signalling has been associated with synaptic defects during development and in neurodegenerative conditions such as Alzheimer’s disease. New studies suggest that the localisation and stability of Fzd receptors play a crucial role in determining Wnt function. Post-translational modifications (PTMs) of Fzd are emerging as an important mechanism that regulates these Wnt receptors. However, only phosphorylation and glycosylation have been described to modulate Fzd function in the central nervous system (CNS). In this review, we discuss the function of Fzd in neuronal circuit connectivity and how PTMs contribute to their function. We also discuss other PTMs, not yet described in the CNS, and how they might modulate the function of Fzd in neuronal connectivity. PTMs could modulate Fzd function by affecting Fzd localisation and stability at the plasma membrane resulting in local effects of Wnt signalling, a feature particularly important in polarised cells such as neurons. Our review highlights the importance of further studies into the role of PTMs on Fzd receptors in the context of neuronal connectivity.
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DOI：
10.1523/jneurosci.4508-10.2010
发表时间：
2010-11-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fenstermaker AG;Prasad AA;Bechara A;Adolfs Y;Tissir F;Goffinet A;Zou Y;Pasterkamp RJ
通讯作者：
Pasterkamp RJ
DOI：
10.1093/cercor/bhw132
发表时间：
2016-07
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
--
作者：
Feng J;Xian Q;Guan T;Hu J;Wang M;Huang Y;So KF;Evans SM;Chai G;Goffinet AM;Qu Y;Zhou L
通讯作者：
Zhou L
影响因子：
64.8
作者：
Bhanot, P;Brink, M;Nusse, R
通讯作者：
Nusse, R
影响因子：
64.8
作者：
Hao, Huai-Xiang;Xie, Yang;Cong, Feng
通讯作者：
Cong, Feng
影响因子：
56.9
作者：
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通讯作者：
Niehrs, Christof