Next Article in Journal
A Novel Analysis of the Peptide Terminome Characterizes Dynamics of Proteolytic Regulation in Vertebrate Skeletal Muscle Under Severe Stress
Next Article in Special Issue
Correction: Baucum II, Anthony J. et al. Proteomic Analysis of the Spinophilin Interactome in Rodent Striatum Following Psychostimulant Sensitization. Proteomes 2018, 6, 53
Previous Article in Journal
Analysis of the Bacterial and Host Proteins along and across the Porcine Gastrointestinal Tract
Previous Article in Special Issue
Proteomic Analysis of the Spinophilin Interactome in Rodent Striatum Following Psychostimulant Sensitization
Open AccessArticle

Sex-Specific Proteomic Changes Induced by Genetic Deletion of Fibroblast Growth Factor 14 (FGF14), a Regulator of Neuronal Ion Channels

1
UTMB MD/PhD Combined Degree Program, University of Texas Medical Branch, Galveston, TX 77555, USA
2
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA
3
Neuroscience Graduate Program, University of Texas Medical Branch, Galveston, TX 77555, USA
4
Biochemistry and Molecular Biology Graduate Program, University of Texas Medical Branch, Galveston, TX 77555, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Proteomes 2019, 7(1), 5; https://doi.org/10.3390/proteomes7010005
Received: 16 November 2018 / Revised: 16 January 2019 / Accepted: 17 January 2019 / Published: 23 January 2019
(This article belongs to the Special Issue Neuroproteomics)
Fibroblast growth factor 14 (FGF14) is a member of the intracellular FGFs, which is a group of proteins involved in neuronal ion channel regulation and synaptic transmission. We previously demonstrated that male Fgf14−/− mice recapitulate the salient endophenotypes of synaptic dysfunction and behaviors that are associated with schizophrenia (SZ). As the underlying etiology of SZ and its sex-specific onset remain elusive, the Fgf14−/− model may provide a valuable tool to interrogate pathways related to disease mechanisms. Here, we performed label-free quantitative proteomics to identify enriched pathways in both male and female hippocampi from Fgf14+/+ and Fgf14−/− mice. We discovered that all of the differentially expressed proteins measured in Fgf14−/− animals, relative to their same-sex wildtype counterparts, are associated with SZ based on genome-wide association data. In addition, measured changes in the proteome were predominantly sex-specific, with the male Fgf14−/− mice distinctly enriched for pathways associated with neuropsychiatric disorders. In the male Fgf14−/− mouse, we found molecular characteristics that, in part, may explain a previously described neurotransmission and behavioral phenotype. This includes decreased levels of ALDH1A1 and protein kinase A (PRKAR2B). ALDH1A1 has been shown to mediate an alternative pathway for gamma-aminobutyric acid (GABA) synthesis, while PRKAR2B is essential for dopamine 2 receptor signaling, which is the basis of current antipsychotics. Collectively, our results provide new insights in the role of FGF14 and support the use of the Fgf14−/− mouse as a useful preclinical model of SZ for generating hypotheses on disease mechanisms, sex-specific manifestation, and therapy. View Full-Text
Keywords: mass spectroscopy; bioinformatics; FGF14; voltage gated channels; schizophrenia; autism; Alzheimer’s Disease; sex-specific differences; synaptic plasticity; cognitive impairment; excitatory/inhibitory tone mass spectroscopy; bioinformatics; FGF14; voltage gated channels; schizophrenia; autism; Alzheimer’s Disease; sex-specific differences; synaptic plasticity; cognitive impairment; excitatory/inhibitory tone
Show Figures

Figure 1

MDPI and ACS Style

Sowers, M.L.; Di Re, J.; Wadsworth, P.A.; Shavkunov, A.S.; Lichti, C.; Zhang, K.; Laezza, F. Sex-Specific Proteomic Changes Induced by Genetic Deletion of Fibroblast Growth Factor 14 (FGF14), a Regulator of Neuronal Ion Channels. Proteomes 2019, 7, 5.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop