Male reproductive gland proteins (mRGPs) impact the physiology and/or behavior of mated females in a broad range of organisms. We sought to identify mRGPs of the yellow fever mosquito, Aedes aegypti, the primary vector of dengue and yellow fever viruses. Earlier studies with Ae. aegypti demonstrated that "matrone" (a partially purified male reproductive accessory gland substance) or male accessory gland fluid injected into virgin female Ae. aegypti affect female sexual refractoriness, blood feeding and digestion, flight, ovarian development, and oviposition. Using bioinformatic comparisons to Drosophila melanogaster accessory gland proteins and mass spectrometry of proteins from Ae. aegypti male accessory glands and ejaculatory ducts (AG/ED) and female reproductive tracts, we identified 63 new putative Ae. aegypti mRGPs. Twenty-one of these proteins were found in the reproductive tract of mated females, but not of virgin females, suggesting that they are transferred from males to females during mating. Most of the putative mRGPs fall into the same protein classes as mRGPs in other organisms, although some appear to be evolving rapidly and lack identifiable homologs in Culex pipiens, Anopheles gambiae, and D. melanogaster. Our results identify candidate male-derived molecules that may have an important influence on behavior, survival and reproduction of female mosquitoes.
Background-Genetic markers in the serotonin transporter are associated with panic disorder. The associated polymorphisms do not include the serotonin transporter-linked polymorphic region and display no obvious functional attributes. A common polymorphism (rs3813034) occurs in one of the two reported polyadenylation signals for the serotonin transporter and is in linkage disequilibrium with the panic disorder-associated markers. If functional, rs3813034 may be the risk factor that explains the association of the serotonin transporter and panic disorder.
Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans.
Adverse early care is associated with attention regulatory problems, but not all so exposed develop attention problems. In a sample of 612 youth (girls=432, M=11.82 yrs, SD=1.5) adopted from institutions (e.g., orphanages) in 25 countries, we examined whether the Val66Met polymorphism of the BDNF gene moderates attention problems associated with the duration of institutional care. Parent-reported attention problem symptoms were collected using the MacArthur Health and Behavior Questionnaire. DNA was genotyped for the BDNF Val66Met (rs6265) SNP. Among youth from SE Asia, the predominant genotype was Val/Met, while among youth from Russia/Europe and Caribbean/South America the predominant genotype was Val/Val. For analysis, youth were grouped as carrying Val/Val or AnyMet alleles. Being female, being from SE Asia, and being younger when adopted were associated with fewer attention regulatory problem symptoms. Youth carrying at least one copy of the Met allele were more sensitive to the duration of deprivation, yielding an interaction that followed a differential susceptibility pattern. Thus, youth with Val/Met or Met/Met genotypes exhibited fewer symptoms than Val/Val genotypes when adoption was very early and more symptoms when adoption occurred later in development. Similar patterns were observed when SE Asian youth and youth from other parts of the world were analyzed separately.
The serotonin transporter (SERT) is a major regulator of serotonergic neurotransmission and anxiety-related behaviors. SERT is expressed in two alternative polyadenylation forms that differ by an evolutionarily conserved element in the 3′ untranslated region of its mRNA. Expression of SERT mRNA containing the distal polyadenylation element is associated with decreased anxiety-related behaviors in mice and humans, suggesting that this element has behaviorally relevant modulatory effects on SERT expression. We have identified heterogeneous nuclear ribonucleoprotein K (hnRNPK), a protein known to integrate multiple signal transduction pathways with gene expression, as a SERT distal polyadenylation element binding protein. This interaction is functionally meaningful because genetic manipulation of hnRNPK alters expression of the SERT protein. Furthermore, the trophic factor S100β induces Srcfamily kinase-mediated tyrosine phosphorylation of hnRNPK and increased SERT expression. These results identify a previously unknown mechanism of regulated SERT expression and provide a putative mechanism by which the SERT distal polyadenylation element modulates anxiety-related behaviors.A lternative polyadenylation creates structural and functional diversity in the expression of protein coding messenger RNA (mRNA) through the formation of mRNA species that differ in the sequence content of their 3′ untranslated regions (UTRs) (1-3). The 3′ UTRs of mRNAs have become recognized as major sources of regulated gene expression through sequence-specific microRNA (miR) and ribonucleoprotein (RNP) binding that can alter the stability, translational activity, and subcellular localization of mRNAs (4-6). As a result, alternative polyadenylation forms of mRNA species may display discrete biological properties (7,8).The serotonin transporter (SERT; SLC6A4) plays a central role in regulating serotonergic neurotransmission, and the mRNA coding for SERT occurs in two phylogenetically conserved alternative polyadenylation forms that differ by the presence or absence of an ∼125-bp element (9, 10). We have reported that expression of the longer, or distal, polyadenylation form of the SERT mRNA confers anxiolytic properties on behavior (11, 12). Specifically, males express higher levels of the distal polyadenylation form of SERT than females, who display a two-to threefold higher risk for anxiety disorders than males; a common polymorphism that is associated with expression of the SERT polyadenylation forms in human postmortem brain is also associated with risk for panic disorder, trait anxiety, and the ability of human subjects to retain fear extinction learning, a validated endophenotype of anxiety and its disorders (11,12). Finally, treatment of mice with the SERTselective antidepressant/anxiolytic drug fluoxetine, which has also been shown to enhance fear extinction retention, increases expression of the distal polyadenylation form of SERT (12,13).To advance understanding of how the SERT distal polyadenylation sequence modulates anxiety-relate...
Fear extinction learning, the ability to reassess a learned cue of danger as safe when it no longer predicts aversive events, is often dysregulated in anxiety disorders. Selective serotonin reuptake inhibitors (SSRI's) enhance neural plasticity and their ability to enhance fear extinction learning may explain their anxiolytic properties. Caloric restriction (CR) has SSRI-like effects on neural plasticity and anxiety-related behavior. We implemented CR in mice to determine its effects on conditioned-fear responses. Wild type and serotonin transporter (SERT) knockout mice underwent CR for 7 days leading to significant weight loss. Mice were then tested for cued fear learning and anxiety-related behavior. CR markedly enhanced fear extinction learning and its retention in adolescent female mice, and adults of both sexes. These effects of CR were absent in SERT knockout mice. Moreover, CR phenocopied behavioral and molecular effects of chronic fluoxetine, but there was no additive effect of CR in fluoxetine-treated mice. These results demonstrate that CR enhances fear extinction learning through a SERT-dependent mechanism. These results may have implications for eating disorders such as anorexia nervosa (AN), in which there is a high prevalence of anxiety before the onset of dietary restriction and support proposals that in AN, CR is a motivated effort to control dysregulated fear responses and elevated anxiety.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.