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Current Topics in Microbiology and... 2012Drosophila melanogaster has a single Adar gene encoding a protein related to mammalian ADAR2 that edits transcripts encoding glutamate receptor subunits. We describe the... (Review)
Review
Drosophila melanogaster has a single Adar gene encoding a protein related to mammalian ADAR2 that edits transcripts encoding glutamate receptor subunits. We describe the structure of the Drosophila Adar locus and use ModENCODE information to supplement published data on Adar gene transcription, and splicing. We discuss the roles of ADAR in Drosophila in terms of the two main types of RNA molecules edited and roles of ADARs as RNA-binding proteins. Site-specific RNA editing events in transcripts encoding ion channel subunits were initially found serendipitously and subsequent directed searches for editing sites and transcriptome sequencing have now led to 972 edited sites being identified in 597 transcripts. Four percent of D. melanogaster transcripts are site-specifically edited and these encode a wide range of largely membrane-associated proteins expressed particularly in CNS. Electrophysiological studies on the effects of specific RNA editing events on ion channel subunits do not suggest that loss of RNA editing events in ion channels consistently produce a particular outcome such as making Adar mutant neurons more excitable. This possibility would have been consistent with neurodegeneration seen in Adar mutant fly brains. A further set of ADAR targets are dsRNA intermediates in siRNA generation, derived from transposons and from structured RNA loci. Transcripts with convergent overlapping 3' ends are also edited and the first discovered instance of RNA editing in Drosophila, in the Rnp4F transcript, is an example. There is no evidence yet to show that Adar antagonizes RNA interference in Drosophila. Evidence has been obtained that catalytically inactive ADAR proteins exert effects on microRNA generation and RNA interference. Whether all effects of inactive ADARs are due to RNA-binding or to even further roles of these proteins remains to be determined.
Topics: Adenosine Deaminase; Animals; Drosophila; Drosophila Proteins; RNA Editing; RNA Interference; Transcription, Genetic
PubMed: 21761288
DOI: 10.1007/82_2011_152 -
Nature Neuroscience Feb 2020Arc, a neuronal gene that is critical for synaptic plasticity, originated through the domestication of retrotransposon Gag genes and mediates intercellular messenger RNA...
Arc, a neuronal gene that is critical for synaptic plasticity, originated through the domestication of retrotransposon Gag genes and mediates intercellular messenger RNA transfer. We report high-resolution structures of retrovirus-like capsids formed by Drosophila dArc1 and dArc2 that have surface spikes and putative internal RNA-binding domains. These data demonstrate that virus-like capsid-forming properties of Arc are evolutionarily conserved and provide a structural basis for understanding their function in intercellular communication.
Topics: Amino Acid Sequence; Animals; Capsid; Drosophila Proteins; Drosophila melanogaster; Protein Conformation
PubMed: 31907439
DOI: 10.1038/s41593-019-0569-y -
Cell Reports Aug 2023Feeding behavior is essential for growth and survival of animals; however, relatively little is known about its intrinsic mechanisms. Here, we demonstrate that Gart is...
Feeding behavior is essential for growth and survival of animals; however, relatively little is known about its intrinsic mechanisms. Here, we demonstrate that Gart is expressed in the glia, fat body, and gut and positively regulates feeding behavior via cooperation and coordination. Gart in the gut is crucial for maintaining endogenous feeding rhythms and food intake, while Gart in the glia and fat body regulates energy homeostasis between synthesis and metabolism. These roles of Gart further impact Drosophila lifespan. Importantly, Gart expression is directly regulated by the CLOCK/CYCLE heterodimer via canonical E-box, in which the CLOCKs (CLKs) in the glia, fat body, and gut positively regulate Gart of peripheral tissues, while the core CLK in brain negatively controls Gart of peripheral tissues. This study provides insight into the complex and subtle regulatory mechanisms of feeding and lifespan extension in animals.
Topics: Animals; Circadian Rhythm; Drosophila melanogaster; Drosophila Proteins; Feeding Behavior; Gene Expression Regulation; Homeostasis
PubMed: 37531254
DOI: 10.1016/j.celrep.2023.112912 -
Developmental Biology Apr 2022The ability of stem cells to divide asymmetrically is crucial for cell-type diversity and tissue homeostasis. Drosophila neural stem cells, also knowns as neuroblasts,... (Review)
Review
The ability of stem cells to divide asymmetrically is crucial for cell-type diversity and tissue homeostasis. Drosophila neural stem cells, also knowns as neuroblasts, utilize asymmetric cell division to self-renew and give rise to differentiated daughter cells. Drosophila neuroblasts relies on the polarized protein complexes on the apical and basal cortex to govern cell polarity and asymmetry. Here, we review recent advances in our understanding of the neuroblast polarity focusing on how actin cytoskeleton, phosphoinositide lipids and liquid-liquid phase separation regulate the asymmetric cell division of Drosophila neuroblasts.
Topics: Animals; Cell Division; Drosophila; Drosophila Proteins; Neural Stem Cells; Neurons
PubMed: 35181298
DOI: 10.1016/j.ydbio.2022.02.006 -
Nature Neuroscience Apr 2024Sleep is thought to be restorative to brain energy homeostasis, but it is not clear how this is achieved. We show here that Drosophila glia exhibit a daily cycle of...
Sleep is thought to be restorative to brain energy homeostasis, but it is not clear how this is achieved. We show here that Drosophila glia exhibit a daily cycle of glial mitochondrial oxidation and lipid accumulation that is dependent on prior wake and requires the Drosophila APOE orthologs NLaz and GLaz, which mediate neuron-glia lipid transfer. In turn, a full night of sleep is required for glial lipid clearance, mitochondrial oxidative recovery and maximal neuronal mitophagy. Knockdown of neuronal NLaz causes oxidative stress to accumulate in neurons, and the neuronal mitochondrial integrity protein, Drp1, is required for daily glial lipid accumulation. These data suggest that neurons avoid accumulation of oxidative mitochondrial damage during wake by using mitophagy and passing damage to glia in the form of lipids. We propose that a mitochondrial lipid metabolic cycle between neurons and glia reflects a fundamental function of sleep relevant for brain energy homeostasis.
Topics: Animals; Neuroglia; Drosophila Proteins; Neurons; Drosophila; Homeostasis; Sleep; Lipids
PubMed: 38360946
DOI: 10.1038/s41593-023-01568-1 -
Genes Feb 2020Behavior is a readout of neural function. Therefore, any difference in behavior among different species is, in theory, an outcome of interspecies diversification in the... (Review)
Review
Behavior is a readout of neural function. Therefore, any difference in behavior among different species is, in theory, an outcome of interspecies diversification in the structure and/or function of the nervous system. However, the neural diversity underlying the species-specificity in behavioral traits and its genetic basis have been poorly understood. In this article, we discuss potential neural substrates for species differences in the courtship pulse song frequency and mating partner choice in the subgroup. We also discuss possible neurogenetic mechanisms whereby a novel behavioral repertoire emerges based on the study of nuptial gift transfer, a trait unique to in the genus . We found that the conserved central circuit composed primarily of -expressing neurons (the -circuit) serves for the execution of courtship behavior, whereas the sensory pathways impinging onto the -circuit or the motor pathways downstream of the -circuit are susceptible to changes associated with behavioral species differences.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Neural Pathways; Neurons; Sexual Behavior, Animal
PubMed: 32024133
DOI: 10.3390/genes11020157 -
Cell Stress & Chaperones Jul 2020Small heat shock proteins (sHsps) are ubiquitous molecular chaperones found in all domains of life, possessing significant roles in protein quality control in cells and... (Review)
Review
Small heat shock proteins (sHsps) are ubiquitous molecular chaperones found in all domains of life, possessing significant roles in protein quality control in cells and assisting the refolding of non-native proteins. They are efficient chaperones against many in vitro protein substrates. Nevertheless, the in vivo native substrates of sHsps are not known. To better understand the functions of sHsps and the mechanisms by which they enhance heat resistance, sHsp-interacting proteins were identified using affinity purification under heat shock conditions. This paper aims at providing some insights into the characteristics of natural substrate proteins of sHsps. It seems that sHsps of prokaryotes, as well as sHsps of some eukaryotes, can bind to a wide range of substrate proteins with a preference for certain functional classes of proteins. Using Drosophila melanogaster mitochondrial Hsp22 as a model system, we observed that this sHsp interacted with the members of ATP synthase machinery. Mechanistically, Hsp22 interacts with the multi-type substrate proteins under heat shock conditions as well as non-heat shock conditions.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Heat-Shock Proteins; Heat-Shock Proteins, Small; Heat-Shock Response; Substrate Specificity
PubMed: 32314314
DOI: 10.1007/s12192-020-01097-x -
Current Biology : CB Sep 2023The needs fulfilled by sleep are unknown, though the effects of insufficient sleep are manifold. To better understand how the need to sleep is sensed and discharged,...
The needs fulfilled by sleep are unknown, though the effects of insufficient sleep are manifold. To better understand how the need to sleep is sensed and discharged, much effort has gone into identifying the neural circuits involved in regulating arousal, especially those that promote sleep. In prevailing models, the dorsal fan-shaped body (dFB) plays a central role in this process in the fly brain. In the present study we manipulated various properties of the dFB including its electrical activity, synaptic output, and endogenous gene expression. In each of these experimental contexts we were unable to identify any effect on sleep that could be unambiguously mapped to the dFB. Furthermore, we found evidence that sleep phenotypes previously attributed to the dFB were caused by genetic manipulations that inadvertently targeted the ventral nerve cord. We also examined expression of two genes whose purported effects have been attributed to functions within a specific subpopulation of dFB neurons. In both cases we found little to no expression in the expected cells. Collectively, our results cast doubt on the prevailing hypothesis that the dFB plays a central role in promoting sleep.
Topics: Animals; Drosophila; Drosophila melanogaster; Drosophila Proteins; Sleep; Sleep Deprivation
PubMed: 37552985
DOI: 10.1016/j.cub.2023.07.043 -
Journal of Innate Immunity 2011Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed...
Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Evolution, Molecular; Gene Expression Regulation; Hemocytes; Immunity, Innate; In Situ Hybridization; Molecular Sequence Data; Mutation; Phylogeny; Sequence Analysis, DNA
PubMed: 21063077
DOI: 10.1159/000321554 -
Epigenetics Nov 2020Ten-eleven Translocation (TET) proteins have emerged as a family of epigenetic regulators that are important during development and have been implicated in various types... (Review)
Review
Ten-eleven Translocation (TET) proteins have emerged as a family of epigenetic regulators that are important during development and have been implicated in various types of cancers. TET is a highly conserved protein that has orthologues in almost all multicellular organisms. Here, we review recent literature on the novel substrate specificity of this family of DNA 5-methylcytosine demethylases on DNA 6-methyladenine and RNA 5-methylcytosine that were first identified in the invertebrate model . We focus on the biological role of these novel epigenetic marks in the fruit fly and mammals and highlight TET proteins' critical function during development specifically in brain development.
Topics: Animals; DNA Methylation; Drosophila; Drosophila Proteins; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Mixed Function Oxygenases
PubMed: 32419604
DOI: 10.1080/15592294.2020.1767323