Intracellular Fibroblast Growth Factor 14: Emerging Risk Factor for Brain Disorders.
Intracellular Fibroblast Growth Factor 14: Emerging Risk Factor for Brain Disorders.
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DOI：
10.3389/fncel.2017.00103
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发表时间：
2017
影响因子：
5.3
通讯作者：
Laezza F
中科院分区：
文献类型：
--
作者：
Di Re J;Wadsworth PA;Laezza F
神经元放电的精细调节依赖于离子通道大分子复合物的完整性。这些受到严格调控的网络的最小干扰可能会导致大脑回路的持续适应不良可塑性。细胞内成纤维细胞生长因子 14 (FGF14) 属于与轴突起始段电压门控 Na+ (Nav) 通道相互作用的蛋白质连接。通过与神经元 Nav 通道（Nav1.1、Nav1.2、Nav1.6）的细胞内 C 端尾部的异构体特异性相互作用，FGF14 控制神经元中的通道门控、轴突靶向和磷酸化，从而影响兴奋性。 FGF14 还参与皮质-中脑边缘回路中的突触传递、可塑性和神经发生，以及认知和情感行为结果。在转化研究中，随着越来越多的 FGF14 与认知和情感领域疾病（如神经退行性疾病、抑郁、焦虑、成瘾行为和最近的精神分裂症）的关联，对 FGF14 的兴趣持续上升，这表明 FGF14 在复杂脑部疾病的病因学中作为汇聚节点的作用。然而，对神经元中 FGF14 功能的全面了解还远未完成，并且可能涉及与 Nav 通道直接调节无关的其他功能。这篇迷你评论文章的目的是总结 FGF14 在复杂脑部疾病中的新作用的研究。
The finely tuned regulation of neuronal firing relies on the integrity of ion channel macromolecular complexes. Minimal disturbances of these tightly regulated networks can lead to persistent maladaptive plasticity of brain circuitry. The intracellular fibroblast growth factor 14 (FGF14) belongs to the nexus of proteins interacting with voltage-gated Na+ (Nav) channels at the axonal initial segment. Through isoform-specific interactions with the intracellular C-terminal tail of neuronal Nav channels (Nav1.1, Nav1.2, Nav1.6), FGF14 controls channel gating, axonal targeting and phosphorylation in neurons effecting excitability. FGF14 has been also involved in synaptic transmission, plasticity and neurogenesis in the cortico-mesolimbic circuit with cognitive and affective behavioral outcomes. In translational studies, interest in FGF14 continues to rise with a growing list of associative links to diseases of the cognitive and affective domains such as neurodegeneration, depression, anxiety, addictive behaviors and recently schizophrenia, suggesting its role as a converging node in the etiology of complex brain disorders. Yet, a full understanding of FGF14 function in neurons is far from being complete and likely to involve other functions unrelated to the direct regulation of Nav channels. The goal of this Mini Review article is to provide a summary of studies on the emerging role of FGF14 in complex brain disorders.