Di Re Jessica, Wadsworth Paul A, Laezza Fernanda
Neuroscience Graduate Program, University of Texas Medical BranchGalveston, TX, USA.
Department of Pharmacology and Toxicology, University of Texas Medical BranchGalveston, TX, USA.
Front Cell Neurosci. 2017 Apr 19;11:103. doi: 10.3389/fncel.2017.00103. eCollection 2017.
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+ (Na) channels at the axonal initial segment. Through isoform-specific interactions with the intracellular C-terminal tail of neuronal Na channels (Na1.1, Na1.2, Na1.6), 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 Na 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.
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。这些严格调控的网络受到的微小干扰都可能导致脑回路持续出现适应不良的可塑性。细胞内成纤维细胞生长因子14（FGF14）属于在轴突起始段与电压门控钠通道相互作用的蛋白质网络。通过与神经元钠通道（Na1.1、Na1.2、Na1.6）的细胞内C末端尾巴进行亚型特异性相互作用，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还参与了皮质 - 中脑边缘回路中的突触传递、可塑性和神经发生，并产生认知和情感行为结果。在转化研究中，随着与认知和情感领域疾病（如神经退行性变、抑郁症、焦虑症、成瘾行为以及最近的精神分裂症）的关联不断增加，对FGF14的兴趣持续上升，这表明它在复杂脑疾病病因中作为一个汇聚节点的作用。然而，对FGF14在神经元中的功能的全面理解还远远不够，并且可能涉及与钠通道直接调节无关的其他功能。这篇小型综述文章的目的是总结关于FGF14在复杂脑疾病中新兴作用的研究。
