Biology subjects

Kaya, A.

Publications and source records attributed to Kaya, A..

17 recordsLinked to original sources

bioRxiv2026

Color-dependent foraging in C. elegans integrates chromoprotein photosensitization with bacterial metabolic cues

Animals rely on color to navigate complex environments, yet how eyeless organisms use chromatic information to guide food choice remains poorly understood. Here, we show that Caenorhabditis elegans exhibits robust color dependent foraging driven by microbial chromophores, preferentially consuming red while avoiding blue chromoprotein expressing bacteria across bacterial backgrounds and wild isolates. This discrimination persists in darkness and independently of photoreceptor, revealing a mechanism beyond canonical photoreception. Purified chromoproteins and bacterial metabolite fractions independently reproduce preference, demonstrating complementary chromatic and post ingestive metabolic cues. Mechanistically, blue chromoproteins generate singlet oxygen, producing oxidative stress and remodeling bacterial tryptophan and pterin metabolism, whereas red food promotes serotonin production and feeding-associated neuropeptide signaling. Disrupting serotonin biosynthesis or neuropeptide processing abolishes color preference. Together, our findings reveal a previously unrecognized, novel sensory strategy in which wavelength-selective pigment photochemistry transforms microbial color into metabolic information that is integrated through gut brain neuroendocrine signaling to guide foraging behavior in an eyeless animal.

molecular biology↗

bioRxiv2026

NPC1 deficiency engages a lysosome - genome - immune program linked to neurodegeneration and cellular aging signatures

Lysosomal dysfunction is a prominent feature of neurodegeneration and aging, yet how primary defects in lysosomal trafficking are converted into progressive cellular decline remains poorly understood. Niemann Pick disease type C (NPC), caused by impaired NPC1 dependent cholesterol export, provides a genetically defined model to address this question. Here, we show that NPC1 deficiency activates a lysosome, genome, immune axis linking cholesterol trafficking failure to neurodegeneration and hallmarks of cellular aging. In Npc1 mutant mice, NPC1 loss triggered DNA damage, neuroinflammation, microglial and astrocytic activation, Purkinje neuron degeneration, and motor dysfunction. Consistently, NPC patient-derived fibroblasts exhibited mitochondrial abnormalities and widespread DNA double-strand breaks. Genome-wide DNA break mapping and transcriptomic analyses revealed extensive genomic instability at regulatory regions, including enrichment of DNA breaks at transcription start sites and G quadruplex associated loci, accompanied by widespread transcriptional reprogramming, activation of innate immune pathways, disruption of fibroblast identity, and induction of cellular aging signatures. We further identify Fingolimod, an FDA approved sphingosine - 1 phosphate receptor modulator, as a potent modifier of this disease network. Fingolimod improved lysosomal cholesterol trafficking, increased LAMP1 abundance, attenuated STING associated inflammatory signaling, normalized mitochondrial function, reduced neuroinflammatory and neurodegenerative phenotypes in Npc1 mutant mice, and broadly shifted disease-associated transcriptional programs toward a healthier state. Extending these findings beyond NPC, Fingolimod improved age-associated phenotypes in C. elegans and prolonged lifespan in aged male mice. Together, these findings identify genome instability and chronic innate immune activation as major downstream consequences of lysosomal cholesterol trafficking failure and establish Fingolimod as a clinically actionable modulator of lysosomal dysfunction, neurodegeneration, and aging-related decline.

molecular biology↗

bioRxiv2025

The competitive interplay of 12-oxophytodienoic acid (OPDA), protein thiols and glutathione

Cis-(+)-12-Oxophytodienoic acid (OPDA) is a bioactive oxylipin and phytohormone participating in regulation of plant stress responses, growth and development. Due to its ,{beta}-unsaturated carbonyl moiety, OPDA covalently binds to free thiol groups by Michael addition. This binding, termed OPDAylation, alters the activity of target proteins, such as cyclophilin 20-3 (EC:5.2.1.8) and thioredoxins, that are essential components of the cellular redox regulatory network. To function as reversible redox regulatory mechanism, OPDAylation should be complemented by a process of de-OPDAylation allowing for fine-tuning of OPDA-dependent regulation. This study explored OPDAylation and de-OPDAylation in vitro with emphasis on involvement of glutathione. OPDA can be transferred from protein to glutathione (GSH), and vice versa. In a competition experiment, OPDAylation of thioredoxins occurred rapidly in the presence of GSH, while over extended incubation times, de-OPDAylation of TRX occurred due to the stoichiometric excess of GSH. These results support the hypothesis that the initial thioredoxin-based OPDAylation is proceeding under kinetic control due to the higher reactivity of the more nucleophilic cysteine moiety in thioredoxin compared to the one of GSH, while the OPDAylation of GSH observed at prolonged incubation time is then a result of a thermodynamically controlled process. De-OPDAylation depends on the proteins sensitivity towards OPDA, the pH and the concentration of excess thiol groups. This likely allows for precise modulation of OPDA amounts, as the rapid modification of protein activity enables subsequent induction of OPDA signaling, whereas de-OPDAylation, triggered by increasing glutathione, increasing cellular reduction or presumably enzymatically, reverses this effect.

biochemistry↗

bioRxiv2025

Boosting Cellular Longevity Through Intracellular ATP Modulation

Mitochondrial dysfunction and declining ATP production are common features of aging, yet whether ATP availability itself directly regulates cellular lifespan. However, the causal relationship between cellular ATP homeostasis and aging has not been established. Here, we developed a synthetic system to manipulate intracellular ATP independently of endogenous energy production by expressing a plasma membrane-targeted nucleotide transporter, NTT1, from the intracellular parasite Encephalitozoon cuniculi in Saccharomyces cerevisiae. NTT1 expression depleted intracellular ATP in the absence of extracellular ATP, whereas ATP supplementation produced robust NTT1-dependent ATP uptake and increased intracellular ATP abundance. ATP availability strongly influenced replicative lifespan: ATP depletion shortened lifespan, whereas ATP supplementation restored and extended lifespan in NTT1-expressing cells. Unexpectedly, extracellular ATP also extended lifespan in wild-type cells that lack ATP import, revealing an NTT1-independent response to extracellular ATP. Transcriptomic analyses showed that NTT1- mediated ATP import suppresses glucose uptake, carbohydrate catabolism, mitochondrial respiration, and autophagy, whereas extracellular ATP elicits a distinct transcriptional response in wild-type cells involving metabolic, mitochondrial, and signaling pathways. Single-cell aging analyses further showed that ATP supplementation extends lifespan across distinct aging trajectories and shifts cells away from the mitochondrial dysfunction-associated aging state. Finally, experiments in cells lacking mitochondrial DNA separated these effects mechanistically: NTT1-associated lifespan phenotypes and high-ATP toxicity required functional mitochondria, whereas extracellular ATP extended lifespan in wild-type cells independently of mitochondrial respiration. Together, these findings demonstrate that ATP availability is a direct regulator of cellular aging and reveal distinct metabolic and extracellular ATP-responsive routes through which cellular energy state influences longevity. SignificanceCellular energy homeostasis is a crucial factor in determining the health and longevity of organisms. While intracellular ATP levels are tightly regulated, the idea that cells can directly take in extracellular ATP to influence metabolism has not been thoroughly explored. In this study, we engineered yeast cells to import external ATP and demonstrated that this approach significantly alters mitochondrial function, metabolic flow, and aging processes. Our findings show that ATP uptake inhibits catabolic pathways and modulates mitochondrial bioenergetics function, thereby extending cellular lifespan through a novel and non-traditional mechanism. This research reveals an unexpected degree of metabolic flexibility and introduces a synthetic biology-based method to reprogram energy metabolism and longevity. The principles established in this study provide a new framework for understanding the role of cellular bioenergetics in aging, highlighting how the modulation of ATP availability can impact metabolic states and lifespan regulation.

molecular biology↗

bioRxiv2024

Application of Multiomics Approach to Investigate the Therapeutic Potentials of Stem Cell-derived Extracellular Vesicle Subpopulations for Alzheimer's Disease

Alzheimers disease (AD) presents a complex interplay of molecular alterations, yet understanding its pathogenesis remains a challenge. In this study, we delved into the intricate landscape of proteome and transcriptome changes in AD brains compared to healthy controls, examining 788 brain samples revealing common alterations at both protein and mRNA levels. Moreover, our analysis revealed distinct protein-level changes in aberrant energy metabolism pathways in AD brains that were not evident at the mRNA level. This suggests that the changes in protein expression could provide a deeper molecular representation of AD pathogenesis. Subsequently, using a comparative proteomic approach, we explored the therapeutic potential of mesenchymal stem cell-derived extracellular vehicles (EVs), isolated through various methods, in mitigating AD-associated changes at the protein level. Our analysis revealed a particular EV-subtype that can be utilized for compensating dysregulated mitochondrial proteostasis in the AD brain. By using network biology approaches, we further revealed the potential regulators of key therapeutic proteins. Overall, our study illuminates the significance of proteome alterations in AD pathogenesis and identifies the therapeutic promise of a specific EV subpopulation with reduced pro-inflammatory protein cargo and enriched proteins to target mitochondrial proteostasis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/593647v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@5bbf24org.highwire.dtl.DTLVardef@161dad2org.highwire.dtl.DTLVardef@1653fdcorg.highwire.dtl.DTLVardef@43c0ba_HPS_FORMAT_FIGEXP M_FIG C_FIG The cross-comparison of transcriptomics and proteomics data from AD brain samples and MSCs-derived EVs uncovers the therapeutic potential of a subpopulation targeting mitochondrial proteostasis and inflammation.

genetics↗

bioRxiv2024

A disease similarity approach identifies short-lived Niemann-Pick type C disease mice with accelerated brain aging as a novel mouse model for Alzheimer's disease and aging research

Since its first description in 1906 by Dr. Alois Alzheimer, Alzheimers disease (AD) has been the most common type of dementia. Initially thought to be caused by age-associated accumulation of plaques, in recent years, research has increasingly associated AD with lysosomal storage and metabolic disorders, and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions. However, the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined. Here, we applied a disease similarity approach to identify unknown molecular targets of AD by using transcriptomic data from congenital diseases known to increase AD risk, namely Down Syndrome, Niemann Pick Disease Type C (NPC), and Mucopolysaccharidoses I. We uncovered common pathways, hub genes, and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of AD pathology, many of which have never been associated with AD. We then investigated common molecular alterations in brain samples from an NPC disease mouse model by juxtaposing them with brain samples of both human and mouse models of AD. Detailed phenotypic and molecular analyses revealed that the NPCmut mouse model can serve as a potential short-lived in vivo model for AD research and for understanding molecular factors affecting brain aging. This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on AD research while highlighting shortcomings and lack of correlation in diverse in vitro models. Considering the lack of an AD mouse model that recapitulates the physiological hallmarks of brain aging, the characterization of a short-lived NPC mouse model will further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of AD from a perspective of accelerated brain aging.

genetics↗

bioRxiv2024

Insight from Wild Yeast Isolates into the Molecular Mechanisms of Lifespan Variation Mediated by Caloric Restriction

Caloric restriction (CR) is known to extend lifespan across different species and holds great promise for preventing human age-onset pathologies. However, two major challenges exist. First, despite extensive research, the mechanisms of lifespan extension in response to CR remain elusive. Second, genetic differences causing variations in response to CR and genetic factors contributing to variability of CR response on lifespan are largely unknown. Here, we took advantage of natural genetic variation across 46 diploid wild yeast isolates of Saccharomyces species and the lifespan variation under CR conditions to uncover the molecular factors associated with CR response types. We identified genes and metabolic pathways differentially regulated in CR-responsive versus non-responsive strains. Our analysis revealed that altered mitochondrial function and activation of GCN4-mediated environmental stress response are inevitably linked to lifespan variation in response to CR and a unique mitochondrial metabolite might be utilized as a predictive marker for CR response rate. In sum, our data suggests that the effects of CR on longevity may not be universal, even among the closely related species or strains of a single species. Since mitochondrial-mediated signaling pathways are evolutionarily conserved, the dissection of related genetic pathways will be relevant to understanding the mechanism by which CR elicits its longevity effect. Author summaryCaloric restriction (CR) is an energy-balanced nutrient intake without malnutrition to reduce food intake by 20-40%. CR leads to distinct metabolic reprogramming and adaptive changes in gene expression and, as a result, increases health and lifespan in various model organisms, from yeast to most likely primates. Besides extending lifespan, CR also holds great promise for treating many human age-onset pathologies, and the molecules underlying its effects are sought as targets of pharmaceutical aging therapeutics. However, despite extensive research, the mechanisms of lifespan extension in response to CR remain elusive. In addition, several studies in different aging models have now demonstrated that the longevity effect of CR can vary dramatically across different genotypes within a population. As such, CR might be beneficial for some yet detrimental for others, and the mechanisms underlying such genotype-dependent variation are not clear. In this study, we meet these challenges by dissecting molecular response to CR in diverse wild isolates of yeast strains, aiming to characterize pathways and molecules mediating CRs effects on replicative lifespan (RLS) diversity. We found that the RLS significantly differs across genetically diverse wild yeast isolates under CR conditions. Examining the relationships among the RLS phenotypes under CR and non-CR conditions, transcript, and metabolite provided insights into the role of mitochondrial functions in CR-mediated lifespan extension.

molecular biology↗

bioRxiv2024

mTORC1 ACTIVATION IN PRESUMED CLASSICAL MONOCYTES:OBSERVED CORRELATES WITH HUMAN SIZE VARIATION AND NEUROPSYCHIATRIC DISEASE

BackgroundGain of function disturbances in nutrient sensing are likely the largest component in human age-related disease. Mammalian target of rapamycin complex 1 (mTORC1) activity affects health span and longevity. The drugs ketamine and rapamycin are effective against chronic pain and depression, and both affect mTORC1 activity. Our objective was to measure phosphorylated p70S6K, a marker for mTORC1 activity, in individuals with psychiatric disease to determine whether phosphorylated p70S6K could predict medication response. MethodsTwenty-seven females provided blood samples in which p70S6K and phosphorylated p70S6K were analyzed. Chart review gathered biometric measurements, clinical phenotypes, and medication response. Questionnaires assessed anxiety, depression, autism traits, and mitochondrial dysfunction, to determine neuropsychiatric disease profiles. Univariate and multivariate statistical analyses were used to identify predictors of medication response. ResultsmTORC1 activity correlated highly with both classical biometrics (height, macrocephaly, pupil distance) and specific neuropsychiatric disease profiles (anxiety and autism). Across all cases, phosphorylated p70S6K was the best predictor for ketamine response, and also the best predictor for rapamycin response in a single instance. ConclusionsThe data illustrates the importance of mTORC1 activity in both observable body structure and medication response. This report suggests that a simple assay may allow cost-effective prediction of medication response.

neuroscience↗

bioRxiv2023

Common molecular signatures between coronavirus infection and Alzheimer's disease reveal targets for drug development

Cognitive decline has been reported as a common consequence of COVID-19, and studies have suggested a link between COVID-19 infection and Alzheimers disease (AD). However, the molecular mechanisms underlying this association remain unclear. To shed light on this link, we conducted an integrated genomic analysis using a novel Robust Rank Aggregation method to identify common transcriptional signatures of the frontal cortex, a critical area for cognitive function, between individuals with AD and COVID-19. We then performed various analyses, including the KEGG pathway, GO ontology, protein-protein interaction, hub gene, gene-miRNA, and gene-transcription factor interaction analyses to identify molecular components of biological pathways that are associated with AD in the brain also show similar changes in severe COVID-19. Our findings revealed the molecular mechanisms underpinning the association between COVID-19 infection and AD development and identified several genes, miRNAs, and TFs that may be targeted for therapeutic purposes. However, further research is needed to investigate the diagnostic and therapeutic applications of these findings.

neuroscience↗

bioRxiv2023

Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites and pathways that regulate lifespan

Altered mitochondrial function is tightly linked to lifespan regulation, but underlying mechanisms remain unclear. Here, we report the chronological and replicative lifespan variation across 168 yeast knock-out strains, each lacking a single nuclear-coded mitochondrial gene, including 144 genes with human homologs, many associated with diseases. We dissected the signatures of observed lifespan differences by analyzing profiles of each strains proteome, lipidome, and metabolome under fermentative and respiratory culture conditions, which correspond to the metabolic states of replicative and chronologically aging cells, respectively. Examination of the relationships among extended longevity phenotypes, protein, and metabolite levels revealed that although many of these nuclear-encoded mitochondrial genes carry out different functions, their inhibition attenuates a common mechanism that controls cytosolic ribosomal protein abundance, actin dynamics, and proteasome function to regulate lifespan. The principles of lifespan control learned through this work may be applicable to the regulation of lifespan in more complex organisms, since many aspects of mitochondrial function are highly conserved among eukaryotes.

genetics↗

bioRxiv2023

Evolutionary transcriptomics reveals longevity mostly driven by polygenic and indirect selection in mammals

The maximum lifespan varies more than 100-fold in mammals. This experiment of nature may uncover of the evolutionary forces and molecular features that define longevity. To understand the relationship between gene expression variation and maximum lifespan, we carried out a comparative transcriptomics analysis of liver, kidney, and brain tissues of 106 mammalian species. We found that expression is largely conserved and very limited genes exhibit common expression patterns with longevity in all the three organs analyzed. However, many pathways, e.g., "Insulin signaling pathway", and "FoxO signaling pathway", show accumulated correlations with maximum lifespan across mammals. Analyses of selection features further reveal that methionine restriction related genes whose expressions associated with longevity, are under strong selection in long-lived mammals, suggesting that a common approach could be utilized by natural selection and artificial intervention to control lifespan. These results suggest that natural lifespan regulation via gene expression is likely to be driven through polygenic model and indirect selection.

evolutionary biology↗

bioRxiv2022

Current Situation of Breeding Bird Species in the Gediz Delta, Turkey

Gediz Delta, one of the most important wetland ecosystems in the Mediterranean Basin, also is one of the most important areas for birds in Turkey. Breeding bird atlas studies were carried out in 2002, and 2006 and extensive breeding species were revealed. In 2021, we conducted an atlas of breeding birds using the same method as previous studies and observed the change over the last 15 years. Bird species seen and heard between May 3 and June 15 in 294 1x1 square kilometres were recorded and classified with internationally accepted breeding codes. Breeding codes were given to 113 species belonging to 48 families throughout the study. Of these, 32 species are classified as possible breeding, 34 species as probable breeding and 47 species as confirmed breeding. Threat factors of species and habitats are grouped under five main topics. According to previous studies, we observed that the number of breeding bird species increased. It is thought that the number of breeding bird species will increase with the elimination of threats and carrying out the necessary restoration works.

zoology↗

bioRxiv2022

G protein βγ subunits bind to and inhibit the function of multiple Qa- and Qb,c-SNARE isoforms.

While the ability of G protein {beta}{gamma} subunits (G{beta}{gamma}) to bind to and functionally inhibit the neuronal SNARE proteins Stx1A, SNAP25, and synaptobrevin in the presence of the calcium sensor synaptotagmin I is well documented, these three SNARE proteins, which form the core SNARE complex for synchronous evoked release in neurons, are but a subset of the larger family of SNARE proteins, which participate in many other exocytic processes within the cell and in other populations of secretory cells throughout the body, from which the release of neurotransmitters, hormones, and other factors is regulated by Gi/o-coupled GPCRs. The ability of G{beta}{gamma} to regulate these processes is unknown. To investigate the feasibility of this mechanism to inhibit SNARE function more broadly, we utilized a series of biochemical assays of binding and function with four Qa-SNAREs (Stx1A, Stx2, Stx3, and Stx4) and four Qb,c-SNAREs (SNAP25, SNAP23, SNAP29, and SNAP47) in tandem with the R-SNARE synaptobrevin, synaptotagmin I, and G{beta}{gamma}. G{beta}{gamma} was found to bind to multiple Qa-SNARE isoforms as well as SNAP23, and inhibit the lipid mixing function of these SNAREs, as well as SNAP29. Together, this data suggests a more broad role for the G{beta}{gamma}-SNARE pathway in the regulation of exocytosis beyond cells that express Stx1A or SNAP25.

biochemistry↗

bioRxiv2022

Evidence that conserved essential genes are enriched for pro-longevity factors

At the cellular level, many aspects of aging are conserved across species. This has been demonstrated by numerous studies in simple model organisms like Saccharomyces cerevisiae, Caenorhabdits elegans, and Drosophila melanogaster. Because most genetic screens examine loss of function mutations or decreased expression of genes through reverse genetics, essential genes have often been overlooked as potential modulators of the aging process. By taking the approach of increasing the expression level of a subset of conserved essential genes, we found that 25% of these genes resulted in increased replicative lifespan in S. cerevisiae. This is greater than the [~]3.5% of genes found to affect lifespan upon deletion, suggesting that activation of essential genes may have a relatively disproportionate effect on increasing lifespan. The results of our experiments demonstrate that essential gene overexpression is a rich, relatively unexplored means of increasing eukaryotic lifespan.

cell biology↗

bioRxiv2022

Rapamycin treatment during development extends lifespan and healthspan

The possibility that pace of development is tightly connected to aging is supported by the fact that the onset of reproduction is associated with lifespan and that many longevity interventions target growth and development. However, it has been unknown whether targeting development with pharmacological intervention can lead to a longer lifespan. To test this possibility, we subjected genetically diverse UMHET3 mice to the mTOR inhibitor rapamycin for the first 45 days of life and followed them up until death. Treated mice grew slower, with most of the deceleration occurring in the first week, and remained smaller for their entire lives. Their reproductive age was delayed but without affecting offspring numbers. The treatment was sufficient to extend the median lifespan by 10%, with the most effect in males, and to preserve better health as measured by frailty index, gait speed, and glucose and insulin tolerance tests. Mechanistically, the liver transcriptome of treated mice was younger at the completion of treatment and stayed younger into the old ages in males. Rapamycin initially reduced DNA methylation age of livers, however, that effect was lost with aging. Analogous to mice, rapamycin exposure only during development robustly extended the lifespan of Daphnia magna as well as reduced their body size, suggesting evolutionary conserved mechanisms of this early life effect. Overall, the results demonstrate that short-term rapamycin treatment during early life is a novel longevity intervention that establishes causality between pace of development and longevity in evolutionary distant organisms.

developmental biology↗

bioRxiv2020

Evolution of Natural Lifespan Variation and Molecular Strategies of Extended Lifespan

To understand the genetic basis and selective forces acting on longevity, it is useful to examine lifespan variation among closely related species, or ecologically diverse isolates of the same species, within a controlled environment. In particular, this approach may lead to understanding mechanisms underlying natural variation in lifespan. Here, we analyzed 76 ecologically diverse wild yeast isolates and discovered a wide diversity of replicative lifespan. Phylogenetic analyses pointed to genes and environmental factors that strongly interact to modulate the observed aging patterns. We then identified genetic networks causally associated with natural variation in replicative lifespan across wild yeast isolates, as well as genes, metabolites and pathways, many of which have never been associated with yeast lifespan in laboratory settings. In addition, a combined analysis of lifespan-associated metabolic and transcriptomic changes revealed unique adaptations to interconnected amino acid biosynthesis, glutamate metabolism and mitochondrial function in long-lived strains. Overall, our multi-omic and lifespan analyses across diverse isolates of the same species shows how gene-environment interactions shape cellular processes involved in phenotypic variation such as lifespan.

genetics↗

bioRxiv2020

Specificity of Gβ and γ subunits to SNARE complex both at rest and after α2aadrenergic receptor stimulation

Though much is known about the various physiological functions of each GPCR and the specificity of G subunits, the specificity of G{beta}{gamma} activated by a given GPCR and activating each effector in vivo is not known. Previously, we identified different G{beta} and G{gamma} subunits interacting specifically with 2a-adrenergic receptors (2aAR). In this study, we examined its in vivo specificity to the soluble NSF attachment proteins (SNARE) complex in adrenergic (auto-2aAR) and non-adrenergic (hetero-2aAR) neurons. We applied a quantitative targeted multiple reaction monitoring proteomic analysis of G{beta} and G{gamma} subunits bound to the SNARE complex, and found only a subset of G{beta} and G{gamma} bound. Without stimulation of auto-2aAR, G{beta}1 and G{gamma}3 interacted with the SNARE complex. When auto-2aAR were activated, G{beta}1, G{beta}2, and G{gamma}3 were found. Further understanding of in vivo G{beta}{gamma} specificity to its effectors provides new insights into the multiplicity of genes for G{beta} and G{gamma}. SummarySpecific G{beta}{gamma} dimers interact with the SNARE complex following presynaptic 2aAR activation in both adrenergic and non-adrenergic neurons.

biochemistry↗