Intracellular Fibroblast Growth Factor 14: Emerging Risk Factor for Brain Disorders

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2017 May 5

PMID 28469558

Citations 45

Authors

Jessica Di Re

Paul A Wadsworth

Fernanda Laezza

Affiliations

Soon will be listed here.

Abstract

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.

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