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Developmental Dynamics : An Official... Sep 2017Signal transduction through multiple distinct pathways regulates and orchestrates the numerous biological processes comprising heart development. This review outlines... (Review)
Review
Signal transduction through multiple distinct pathways regulates and orchestrates the numerous biological processes comprising heart development. This review outlines the roles of the FGFR, EGFR, Wnt, BMP, Notch, Hedgehog, Slit/Robo, and other signaling pathways during four sequential phases of Drosophila cardiogenesis-mesoderm migration, cardiac mesoderm establishment, differentiation of the cardiac mesoderm into distinct cardiac cell types, and morphogenesis of the heart and its lumen based on the proper positioning and cell shape changes of these differentiated cardiac cells-and illustrates how these same cardiogenic roles are conserved in vertebrates. Mechanisms bringing about the regulation and combinatorial integration of these diverse signaling pathways in Drosophila are also described. This synopsis of our present state of knowledge of conserved signaling pathways in Drosophila cardiogenesis and the means by which it was acquired should facilitate our understanding of and investigations into related processes in vertebrates. Developmental Dynamics 246:641-656, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Cell Differentiation; Drosophila; Drosophila Proteins; Gene Expression Regulation, Developmental; Heart; Signal Transduction
PubMed: 28598558
DOI: 10.1002/dvdy.24530 -
Methods in Molecular Biology (Clifton,... 2022Proteins are typically not expressed homogeneously in all cells of a complex organism. Within cells, proteins can dynamically change locations, be transported to their...
Proteins are typically not expressed homogeneously in all cells of a complex organism. Within cells, proteins can dynamically change locations, be transported to their destinations, or be degraded upon external signals. Thus, revealing the cellular and subcellular localizations as well as the temporal dynamics of a protein provides important insights into the possible function of the studied protein. Tagging a protein of interest with a genetically encoded fluorophore enables us to follow its expression dynamics in the living organism. Here, we summarize the genetic resources available for tagged Drosophila proteins that assist in studying protein expression and dynamics. We also review the various techniques used in the past and at present to tag a protein of interest with a genetically encoded fluorophore. Comparing the pros and cons of the various techniques guides the reader to judge the suitable applications possible with these tagged proteins in Drosophila.
Topics: Animals; CRISPR-Cas Systems; Drosophila; Drosophila Proteins; Fluorescent Dyes
PubMed: 35980582
DOI: 10.1007/978-1-0716-2541-5_12 -
Methods in Molecular Biology (Clifton,... 2022Binary expression systems are useful genetic tools for experimentally labeling or manipulating the function of defined cells. The Q-system is a repressible binary... (Review)
Review
Binary expression systems are useful genetic tools for experimentally labeling or manipulating the function of defined cells. The Q-system is a repressible binary expression system that consists of a transcription factor QF (and the recently improved QF2/QF2), the inhibitor QS, a QUAS-geneX effector, and a drug that inhibits QS (quinic acid). The Q-system can be used alone or in combination with other binary expression systems, such as GAL4/UAS and LexA/LexAop. In this review chapter, we discuss the past, present, and future of the Q-system for applications in Drosophila and other organisms. We discuss the in vivo application of the Q-system for transgenic labeling, the modular nature of QF that allows chimeric or split transcriptional activators to be developed, its temporal control by quinic acid, new methods to generate QF2 reagents, intersectional expression labeling, and its recent adoption into many emerging experimental species.
Topics: Animals; Animals, Genetically Modified; Drosophila; Drosophila Proteins; Quinic Acid; Transcription Factors; Transgenes
PubMed: 35980572
DOI: 10.1007/978-1-0716-2541-5_2 -
Biomolecules Jan 2022Notch is a developmental receptor, conserved in the evolution of the metazoa, which regulates cell fate proliferation and survival in numerous developmental contexts,... (Review)
Review
Notch is a developmental receptor, conserved in the evolution of the metazoa, which regulates cell fate proliferation and survival in numerous developmental contexts, and also regulates tissue renewal and repair in adult organisms. Notch is activated by proteolytic removal of its extracellular domain and the subsequent release of its intracellular domain, which then acts in the nucleus as part of a transcription factor complex. Numerous regulatory mechanisms exist to tune the amplitude, duration and spatial patterning of this core signalling mechanism. In , Deltex (Dx) and Suppressor of dx (Su(dx)) are E3 ubiquitin ligases which interact with the Notch intracellular domain to regulate its endocytic trafficking, with impacts on both ligand-dependent and ligand-independent signal activation. Homologues of Dx and Su(dx) have been shown to also interact with one or more of the four mammalian Notch proteins and other target substrates. Studies have shown similarities, specialisations and diversifications of the roles of these Notch regulators. This review collates together current research on vertebrate Dx and Su(dx)-related proteins, provides an overview of their various roles, and discusses their contributions to cell fate regulation and disease.
Topics: Animals; Drosophila Proteins; Endocytosis; Humans; Mammals; Membrane Proteins; Receptors, Notch; Ubiquitin-Protein Ligases
PubMed: 35204725
DOI: 10.3390/biom12020224 -
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 -
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 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 -
Advances in Experimental Medicine and... 2018Pioneering cell aggregation experiments from the Artavanis-Tsakonas group in the late 1980's localized the core ligand recognition sequence in the Drosophila Notch... (Review)
Review
Pioneering cell aggregation experiments from the Artavanis-Tsakonas group in the late 1980's localized the core ligand recognition sequence in the Drosophila Notch receptor to epidermal growth factor-like (EGF) domains 11 and 12. Since then, advances in protein expression, structure determination methods and functional assays have enabled us to define the molecular basis of the core receptor/ligand interaction and given new insights into the architecture of the Notch complex at the cell surface. We now know that Notch EGF11 and 12 interact with the Delta/Serrate/LAG-2 (DSL) and C2 domains of ligand and that membrane-binding, together with additional protein-protein interactions outside the core recognition domains, are likely to fine-tune generation of the Notch signal. Furthermore, structure determination of O-glycosylated variants of Notch alone or in complex with receptor fragments, has shown that these sugars contribute directly to the binding interface, as well as to stabilizing intra-molecular domain structure, providing some mechanistic insights into the observed modulatory effects of O-glycosylation on Notch activity.Future challenges lie in determining the complete extracellular architecture of ligand and receptor in order to understand (i) how Notch/ligand complexes may form at the cell surface in response to physiological cues, (ii) the role of lipid binding in stabilizing the Notch/ligand complex, (iii) the impact of O-glycosylation on binding and signalling and (iv) to dissect the different pathologies that arise as a consequence of mutations that affect proteins involved in the Notch pathway.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Glycosylation; Ligands; Protein Domains; Receptors, Notch; Signal Transduction
PubMed: 30030820
DOI: 10.1007/978-3-319-89512-3_2 -
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 -
FEBS Letters Apr 2015Most of our knowledge on protein tyrosine phosphatases (PTPs) is derived from human pathologies and mouse knockout models. These models largely correlate well with human... (Review)
Review
Most of our knowledge on protein tyrosine phosphatases (PTPs) is derived from human pathologies and mouse knockout models. These models largely correlate well with human disease phenotypes, but can be ambiguous due to compensatory mechanisms introduced by paralogous genes. Here we present the analysis of the PTP complement of the fruit fly and the complementary view that PTP studies in Drosophila will accelerate our understanding of PTPs in physiological and pathological conditions. With only 44 PTP genes, Drosophila represents a streamlined version of the human complement. Our integrated analysis places the Drosophila PTPs into evolutionary and functional contexts, thereby providing a platform for the exploitation of the fly for PTP research and the transfer of knowledge onto other model systems.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Evolution, Molecular; Humans; Mice; Multigene Family; Mutation; Phylogeny; Protein Tyrosine Phosphatases
PubMed: 25771859
DOI: 10.1016/j.febslet.2015.03.005