N-glycosylation in regulation of the nervous system.
N-glycosylation in regulation of the nervous system.
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DOI：
10.1007/978-1-4939-1154-7_17
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发表时间：
2014
影响因子：
--
通讯作者：
Panin, Vladislav M
中科院分区：
文献类型：
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作者：
Scott, Hilary;Panin, Vladislav M
蛋白质N-糖基化可以通过影响参与神经系统发育和生理的糖蛋白的功能，以多种方式影响神经系统。N-葡聚糖对神经发育的不同方面的重要性已经得到了很好的证明。例如，在发育过程中，一些N-连接的碳水化合物结构被发现在神经细胞黏附和轴突靶向方面发挥关键作用。同时，糖基化在神经生理学调节中的作用仍然知之甚少。最近的研究表明，N-糖基化参与了神经传递的调节，揭示了多糖在突触过程和神经兴奋性控制中的新作用。N-多糖被发现显著影响几种类型的突触蛋白的功能，这些突触蛋白参与突触传递的关键步骤，包括神经递质的释放、接收和摄取。糖基化还调节一些通道蛋白，如控制对环境刺激反应的Trp通道和电压门控离子通道，这是神经元兴奋性的主要决定因素。唾液酸化的碳水化合物结构在电压门控离子通道的调节中起着特别重要的作用。唾液酸似乎通过几种机制影响通道功能，包括电荷相互作用，以及可能涉及空间位阻效应和与其他分子相互作用的其他相互作用。实验还表明，葡聚糖的某些结构特征对其功能可能特别重要。由于不同细胞类型之间的糖链结构可能有很大的不同，并且取决于细胞的代谢状态，因此使用体内方法分析糖链的功能是很重要的。虽然神经系统的复杂性和糖基化途径的错综复杂会给脊椎动物的体内实验造成严重的障碍，但最近的研究表明，更简单和更容易实验处理的模式生物，如果蝇，应该为阐明神经系统中进化上保守的N-糖基化功能提供重要的优势。
Protein N-glycosylation can influence the nervous system in a variety of ways by affecting functions of glycoproteins involved in nervous system development and physiology. The importance of N-glycans for different aspects of neural development has been well documented. For example, some N-linked carbohydrate structures were found to play key roles in neural cell adhesion and axonal targeting during development. At the same time, the involvement of glycosylation in the regulation of neural physiology remains less understood. Recent studies have implicated N-glycosylation in the regulation of neural transmission, revealing novel roles of glycans in synaptic processes and the control of neural excitability. N-Glycans were found to markedly affect the function of several types of synaptic proteins involved in key steps of synaptic transmission, including neurotransmitter release, reception and uptake. Glycosylation also regulates a number of channel proteins, such as TRP channels that control responses to environmental stimuli and voltage-gated ion channels, the principal determinants of neuronal excitability. Sialylated carbohydrate structures play a particularly prominent part in the modulation of voltage gated ion channels. Sialic acids appear to affect channel functions via several mechanisms, including charge interactions, as well as other interactions that probably engage steric effects and interactions with other molecules. Experiments also indicated that some structural features of glycans can be particularly important for their function. Since glycan structures can vary significantly between different cell types and depends on the metabolic state of the cell, it is important to analyze glycan functions using in vivo approaches. While the complexity of the nervous system and intricacies of glycosylation pathways can create serious obstacles for in vivo experiments in vertebrates, recent studies have indicated that more simple and experimentally tractable model organisms like Drosophila should provide important advantages for elucidating evolutionarily conserved functions of N-glycosylation in the nervous system.