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Current Biology : CB Jun 2015Schimizzi and Longmore summarise what we know about Ajuba LIM-domain proteins and their various subcellular roles.
Schimizzi and Longmore summarise what we know about Ajuba LIM-domain proteins and their various subcellular roles.
Topics: Animals; Drosophila Proteins; LIM Domain Proteins; Signal Transduction
PubMed: 26035782
DOI: 10.1016/j.cub.2015.02.034 -
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 -
Current Topics in Developmental Biology 2022The molecular complexes underlying planar cell polarity (PCP) were first identified in Drosophila through analysis of mutant phenotypes in the adult cuticle and the... (Review)
Review
The molecular complexes underlying planar cell polarity (PCP) were first identified in Drosophila through analysis of mutant phenotypes in the adult cuticle and the orientation of associated polarized protrusions such as wing hairs and sensory bristles. The same molecules are conserved in vertebrates and are required for the localization of polarized protrusions such as primary or sensory cilia and the orientation of hair follicles. Not only is PCP signaling required to align cellular structures across a tissue, it is also required to coordinate movement during embryonic development and adult homeostasis. PCP signaling allows cells to interpret positional cues within a tissue to move in the appropriate direction and to coordinate this movement with their neighbors. In this review we outline the molecular basis of the core Wnt-Frizzled/PCP pathway, and describe how this signaling orchestrates collective motility in Drosophila and vertebrates. Here we cover the paradigms of ommatidial rotation and border cell migration in Drosophila, and convergent extension in vertebrates. The downstream cell biological processes that underlie polarized motility include cytoskeletal reorganization, and adherens junctional and extracellular matrix remodeling. We discuss the contributions of these processes in the respective cell motility contexts. Finally, we address examples of individual cell motility guided by PCP factors during nervous system development and in cancer disease contexts.
Topics: Animals; Cell Movement; Cell Polarity; Drosophila; Drosophila Proteins; Vertebrates; Wnt Signaling Pathway
PubMed: 35817505
DOI: 10.1016/bs.ctdb.2022.03.006 -
Genetics Sep 2020Key discoveries in have shaped our understanding of cellular "enhancers." With a special focus on the fly, this chapter surveys properties of these adaptable... (Review)
Review
Key discoveries in have shaped our understanding of cellular "enhancers." With a special focus on the fly, this chapter surveys properties of these adaptable -regulatory elements, whose actions are critical for the complex spatial/temporal transcriptional regulation of gene expression in metazoa. The powerful combination of genetics, molecular biology, and genomics available in has provided an arena in which the developmental role of enhancers can be explored. Enhancers are characterized by diverse low- or high-throughput assays, which are challenging to interpret, as not all of these methods of identifying enhancers produce concordant results. As a model metazoan, the fly offers important advantages to comprehensive analysis of the central functions that enhancers play in gene expression, and their critical role in mediating the production of phenotypes from genotype and environmental inputs. A major challenge moving forward will be obtaining a quantitative understanding of how these -regulatory elements operate in development and disease.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Enhancer Elements, Genetic; Genetic Techniques; Transcription Factors; Transcriptional Activation
PubMed: 32878914
DOI: 10.1534/genetics.120.301370 -
Current Opinion in Neurobiology Apr 2022The representation of contextual information peripheral to a salient stimulus is central to an animal's ability to correctly interpret and flexibly respond to that... (Review)
Review
The representation of contextual information peripheral to a salient stimulus is central to an animal's ability to correctly interpret and flexibly respond to that stimulus. While the computations and circuits underlying the context-dependent modulation of stimulus-response pairings have typically been studied in vertebrates, the genetic tractability, numeric simplification, and well-characterized connectivity patterns of the Drosophila melanogaster brain have facilitated circuit-level insights into contextual processing. Recent studies in flies reveal the neuronal mechanisms that create flexible context-dependent behavioral responses to sensory events in conditions of predation threat, feeding regulation, and social interaction.
Topics: Animals; Behavior, Animal; Brain; Drosophila; Drosophila Proteins; Drosophila melanogaster
PubMed: 35286864
DOI: 10.1016/j.conb.2022.02.003 -
Current Biology : CB Oct 2021Animals must express the appropriate behavior that meets their most pressing physiological needs and their environmental context. However, it is currently unclear how...
Animals must express the appropriate behavior that meets their most pressing physiological needs and their environmental context. However, it is currently unclear how alternative behavioral options are evaluated and appropriate actions are prioritized. Here, we describe how fruit flies choose between feeding and courtship; two behaviors necessary for survival and reproduction. We show that sex- and food-deprived male flies prioritize feeding over courtship initiation, and manipulation of food quality or the animal's internal state fine-tunes this decision. We identify the tyramine signaling pathway as an essential mediator of this decision. Tyramine biosynthesis is regulated by the fly's nutritional state and acts as a satiety signal, favoring courtship over feeding. Tyramine inhibits a subset of feeding-promoting tyramine receptor (TyrR)-expressing neurons and activates P1 neurons, a known command center for courtship. Conversely, the perception of a nutritious food source activates TyrR neurons and inhibits P1 neurons. Therefore, TyrR and P1 neurons are oppositely modulated by starvation, via tyramine levels, and food availability. We propose that antagonistic co-regulation of neurons controlling alternative actions is key to prioritizing competing drives in a context- dependent manner.
Topics: Animals; Courtship; Drosophila; Drosophila Proteins; Drosophila melanogaster; Male; Neurons; Sexual Behavior, Animal; Tyramine
PubMed: 34358444
DOI: 10.1016/j.cub.2021.07.029 -
International Journal of Molecular... Jul 2022Memories are lasting representations over time of associations between stimuli or events. In general, the relatively slow consolidation of memories requires protein... (Review)
Review
Memories are lasting representations over time of associations between stimuli or events. In general, the relatively slow consolidation of memories requires protein synthesis with a known exception being the so-called Anesthesia Resistant Memory (ARM) in Drosophila. This protein synthesis-independent memory type survives amnestic shocks after a short, sensitive window post training, and can also emerge after repeated cycles of training in a negatively reinforced olfactory conditioning task, without rest between cycles (massed conditioning-MC). We discussed operational and molecular mechanisms that mediate ARM and differentiate it from protein synthesis-dependent long-term memory (LTM) in Drosophila. Based on the notion that ARM is unlikely to specifically characterize Drosophila, we examined protein synthesis and MC-elicited memories in other species and based on intraspecies shared molecular components and proposed potential relationships of ARM with established memory types in Drosophila and vertebrates.
Topics: Anesthesia; Animals; Drosophila; Drosophila Proteins; Drosophila melanogaster; Memory; Memory, Long-Term
PubMed: 35955662
DOI: 10.3390/ijms23158527 -
Current Biology : CB Oct 2017Fukaya and Levine explain the basic features of the genetic phenomenon of transvection, a special class of genetic complementation of mutant alleles on homologous...
Fukaya and Levine explain the basic features of the genetic phenomenon of transvection, a special class of genetic complementation of mutant alleles on homologous chromosomes.
Topics: Alleles; Animals; Drosophila Proteins; Drosophila melanogaster; Gene Expression
PubMed: 29017034
DOI: 10.1016/j.cub.2017.08.001 -
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 -
Seminars in Cell & Developmental Biology Sep 2017Spectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like... (Review)
Review
Spectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which are responsible for an enormous breadth of cellular functions. These functions are related to the regulation of actin, microtubules, intermediate filaments, intracellular organelles, cell adhesions and signalling processes during the development and maintenance of a wide variety of tissues. To gain a deeper understanding of this enormous functional diversity, invertebrate genetic model organisms, such as the fruit fly Drosophila, can be used to develop concepts and mechanistic paradigms that can inform the investigation in higher animals or humans. Here we provide a comprehensive overview of our current knowledge of the Drosophila spectraplakin Short stop (Shot). We describe its functional domains and isoforms and compare them with those of the mammalian spectraplakins dystonin and MACF1. We then summarise its roles during the development and maintenance of the nervous system, epithelia, oocytes and muscles, taking care to compare and contrast mechanistic insights across these functions in the fly, but especially also with related functions of dystonin and MACF1 in mostly mammalian contexts. We hope that this review will improve the wider appreciation of how work on Drosophila Shot can be used as an efficient strategy to promote the fundamental concepts and mechanisms that underpin spectraplakin functions, with important implications for biomedical research into human disease.
Topics: Animals; Axon Guidance; Drosophila Proteins; Drosophila melanogaster; Mammals; Microfilament Proteins; Sequence Homology, Amino Acid; Synapses
PubMed: 28579450
DOI: 10.1016/j.semcdb.2017.05.019