共查询到20条相似文献,搜索用时 31 毫秒
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Sphingolipids are important structural components of membranes that delimit the boundaries of cellular compartments, cells and organisms. They play an equally important role as second messengers, and transduce signals across or within the compartments they define to initiate physiological changes during development, differentiation and a host of other cellular events. For well over a century Drosophila melanogaster has served as a useful model organism to understand some of the fundamental tenets of development, differentiation and signaling in eukaryotic organisms. Directed approaches to study sphingolipid biology in Drosophila have been initiated only recently. Nevertheless, earlier phenotypic studies conducted on genes of unknown biochemical function have recently been recognized as mutants of enzymes of sphingolipid metabolism. Genome sequencing and annotation have aided the identification of homologs of recently discovered genes. Here we present an overview of studies on enzymes of the de novo sphingolipid biosynthetic pathway, known mutants and their phenotypic characterization in Drosophila.Received 14 June 2004; received after revision 15 August 2004; accepted 21 August 2004 相似文献
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Véronique Morel Simon Lepicard Alexandre N. Rey Marie-Laure Parmentier Laurent Schaeffer 《Cellular and molecular life sciences : CMLS》2014,71(17):3363-3379
Nesprin-1 is a core component of a protein complex connecting nuclei to cytoskeleton termed LINC (linker of nucleoskeleton and cytoskeleton). Nesprin-1 is anchored to the nuclear envelope by its C-terminal KASH domain, the disruption of which has been associated with neuronal and neuromuscular pathologies, including autosomal recessive cerebellar ataxia and Emery–Dreifuss muscular dystrophy. Here, we describe a new and unexpected role of Drosophila Nesprin-1, Msp-300, in neuromuscular junction. We show that larvae carrying a deletion of Msp-300 KASH domain (Msp-300 ?KASH ) present a locomotion defect suggestive of a myasthenia, and demonstrate the importance of muscle Msp-300 for this phenotype, using tissue-specific RNAi knock-down. We show that Msp-300 ?KASH mutants display abnormal neurotransmission at the larval neuromuscular junction, as well as an imbalance in postsynaptic glutamate receptor composition with a decreased percentage of GluRIIA-containing receptors. We could rescue Msp-300 ?KASH locomotion phenotypes by GluRIIA overexpression, suggesting that the locomotion impairment associated with the KASH domain deletion is due to a reduction in junctional GluRIIA. In summary, we found that Msp-300 controls GluRIIA density at the neuromuscular junction. Our results suggest that Drosophila is a valuable model for further deciphering how Nesprin-1 and LINC disruption may lead to neuronal and neuromuscular pathologies. 相似文献
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Park S Park SH Baek JY Jy YJ Kim KS Roth J Cho JW Choe KM 《Cellular and molecular life sciences : CMLS》2011,68(20):3377-3384
Modification of nuclear and cytosolic proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) is ubiquitous in cells. The in vivo function of the protein O-GlcNAcylation, however, is not well understood. Here, we manipulated the cellular O-GlcNAcylation level in Drosophila and found that it promotes developmental growth by enhancing insulin signaling. This increase in growth is due mainly to
cell growth and not to cell proliferation. Our data suggest that the increase in the insulin signaling activity is mediated,
at least in part, through O-GlcNAcylation of Akt. These results indicate that O-GlcNAcylation is one of the crucial mechanisms involved in control of insulin signaling during Drosophila development. 相似文献
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Assel Mussabekova Laurent Daeffler Jean-Luc Imler 《Cellular and molecular life sciences : CMLS》2017,74(11):2039-2054
The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations. 相似文献
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Galyna Sidyelyeva Christian Wegener Brian P. Schoenfeld Aaron J. Bell Nicholas E. Baker Sean M. J. McBride Lloyd D. Fricker 《Cellular and molecular life sciences : CMLS》2010,67(17):2991-3004
Metallocarboxypeptidase D (CPD) functions in protein and peptide processing. The Drosophila CPD svr gene undergoes alternative splicing, producing forms containing 1–3 active or inactive CP domains. To investigate the function of the various CP domains, we created transgenic flies expressing specific forms of CPD in the embryonic-lethal svr PG33 mutant. All constructs containing an active CP domain rescued the lethality with varying degrees, and full viability required inactive CP domain-3. Transgenic flies overexpressing active CP domain-1 or -2 were similar to each other and to the viable svr mutants, with pointed wing shape, enhanced ethanol sensitivity, and decreased cold sensitivity. The transgenes fully compensated for a long-term memory deficit observed in the viable svr mutants. Overexpression of CP domain-1 or -2 reduced the levels of Lys/Arg-extended adipokinetic hormone intermediates. These findings suggest that CPD domains-1 and -2 have largely redundant functions in the processing of growth factors, hormones, and neuropeptides. 相似文献
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Insulin signaling regulates lifespan, reproduction, metabolic homeostasis, and resistance to stress in the adult organism.
In Drosophila, there are seven insulin-like peptides (DILP1–7). Three of these (DILP2, 3 and 5) are produced in median neurosecretory cells
of the brain, designated IPCs. Previous work has suggested that production or release of DILPs in IPCs can be regulated by
a factor secreted from the fat body as well as by neuronal GABA or short neuropeptide F. There is also evidence that serotonergic
neurons may regulate IPCs. Here, we investigated mechanisms by which serotonin may regulate the IPCs. We show that the IPCs
in adult flies express the 5-HT1A, but not the 5-HT1B or 5-HT7 receptors, and that processes of serotonergic neurons impinge on the IPC branches. Knockdown of 5-HT1A in IPCs by targeted RNA interference (RNAi) leads to increased sensitivity to heat, prolonged recovery after cold knockdown
and decreased resistance to starvation. Lipid metabolism is also affected, but no effect on growth was seen. Furthermore,
we show that DILP2-immunolevels in IPCs increase after 5-HT1A knockdown; this is accentuated by starvation. Heterozygous 5-HT1A mutant flies display the same phenotype in all assays, as seen after targeted 5-HT1A RNAi, and flies fed the 5-HT1A antagonist WAY100635 display reduced lifespan at starvation. Our findings suggest that serotonin acts on brain IPCs via the
5-HT1A receptor, thereby affecting their activity and probably insulin signaling. Thus, we have identified a second inhibitory pathway
regulating IPC activity in the Drosophila brain. 相似文献
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J. Bohrmann 《Cellular and molecular life sciences : CMLS》1997,53(8):652-662
During mid-oogenesis of Drosophila, cyto plasmic particles are transported within the nurse cells and through ring canals (cytoplasmic bridges) into the oocyte
by means of a microfilament-dependent mecha nism. Video-intensified fluorescence timelapse mi croscopy, in combination with
microinjections of antibodies directed against Drosophila 95F myosin, have revealed that this unconventional myosin of class VI is involved in the transport processes. The results
indicate that certain cytoplasmic particles in the nurse cells move along microfilaments due to their direct association with
myosin VI motors. Additional myosin- VI molecules located at the rim of the ring canals seem to be involved in particle transport
into the oocyte. Microinjected mitochondria-specific dyes have revealed that some of these particles are mitochondria.
Received 3 April 1997; received after revision 5 May 1997; accepted 27 May 1997 相似文献
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Apical–basal polarity is an important characteristic of epithelia and Drosophila neural stem cells. The conserved Par complex, which consists of the atypical protein kinase C and the scaffold proteins Baz and Par6, is a key player in the establishment of apical–basal cell polarity. Membrane recruitment of Baz has been reported to be accomplished by several mechanisms, which might function in redundancy, to ensure the correct localization of the complex. However, none of the described interactions was sufficient to displace the protein from the apical junctions. Here, we dissected the role of the oligomerization domain and the lipid-binding motif of Baz in vivo in the Drosophila embryo. We found that these domains function in redundancy to ensure the apical junctional localization of Baz: inactivation of only one domain is not sufficient to disrupt the function of Baz during apical–basal polarization of epithelial cells and neural stem cells. In contrast, mutation of both domains results in a strongly impaired protein stability and a phenotype characterized by embryonic lethality and an impaired apical–basal polarity in the embryonic epithelium and neural stem cells, resembling a baz-loss of function allele. Strikingly, the binding of Baz to the transmembrane proteins E-Cadherin, Echinoid, and Starry Night was not affected in this mutant protein. Our findings reveal a redundant function of the oligomerization and the lipid-binding domain, which is required for protein stability, correct subcellular localization, and apical–basal cell polarization. 相似文献
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Anita Pruzan L. Ehrman Ira Perelle Joan Probber 《Cellular and molecular life sciences : CMLS》1979,35(8):1023-1025
Summary
Drosophila females modify their choice of mates after an initial mating experience. The altered choices correspond to selective pressures within strains (D. pseudoobscura), semispecies (D. paulistorum), and full species (D. melanogaster andD. simulans) and indicate a learned component in sexual selection. 相似文献
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Royet J 《Cellular and molecular life sciences : CMLS》2011,68(22):3651-3660
Insects mostly develop on decaying and contaminated organic matter and often serve as vectors of biologically transmitted
diseases by transporting microorganisms to the plant and animal hosts. As such, insects are constantly ingesting microorganisms,
a small fraction of which reach their epithelial surfaces, mainly their digestive tract, where they can establish relationships
ranging from symbiosis to mutualism or even parasitism. Understanding the tight physical, genetic, and biochemical interactions
that takes place between intestinal epithelia and either resident or infectious microbes has been a long-lasting objective
of the immunologist. Research in this field has recently been re-vitalized with the development of deep sequencing techniques,
which allow qualitative and quantitative characterization of gut microbiota. Interestingly, the recent identification of regenerative
stem cells in the Drosophila gut together with the initial characterization of Drosophila gut microbiota have opened up new avenues of study aimed at understanding the mechanisms that regulate the dialog between
the Drosophila gut epithelium and its microbiota of this insect model. The fact that some of the responses are conserved across species
combined with the power of Drosophila genetics could make this organism model a useful tool to further elucidate some aspects of the interaction occurring between
the microbiota and the human gut. 相似文献
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R. B. Imberski W. H. Sofer H. Ursprung 《Cellular and molecular life sciences : CMLS》1968,24(5):504-505
Zusammenfassung
Drosophila besitzt Alkoholdehydrogenase in mehreren elektrophoretisch trennbaren molekularen Formen. Durch Anwendung von Acrylamid-Elektrophorese bei 2 verschiedenen Gel-Konzentrationen haben wir nachgewiesen, dass diese verschiedenen Isozyme sich nicht in ihrer Molekulargrösse unterscheiden und deshalb nicht Aggregate darstellen.
Work supported by NIH Training Grant No. HD 139-01 and NSF Grant No. GB-4451. 相似文献
Work supported by NIH Training Grant No. HD 139-01 and NSF Grant No. GB-4451. 相似文献
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Royet J 《Cellular and molecular life sciences : CMLS》2004,61(5):537-546
Over the past years, parallel studies conducted in mammals and flies have emphasized the existence of common mechanisms regulating the vertebrate and invertebrate innate immune systems. This culminated in the discovery of the central role of the Toll pathway in Drosophila immunity and in the implication of Toll-like receptors (TLRs)/interleukin-1(IL-1) in the mammalian innate immune response. In spite of clear similarities, such as shared intracellular pathway components, important divergences are expected between the two groups, whose last common ancestor lived more than half a billion years ago. The most obvious discrepancies lie in the mode of activation of the signalling receptors by microorganisms. In mammals, TLRs are part of protein complexes which directly recognize microbe-associated patterns, whereas Drosophila Toll functions like a classical cytokine receptor rather than a pattern recognition receptor. Recent studies demonstrate that members of the evolutionarily conserved peptidoglycan recognition protein family play an essential role in microbial sensing during immune response of Drosophila.Received 26 June 2003; received after revision 29 July 2003; accepted 25 August 2003 相似文献
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Stephanie Oertel Klaus Scholich Andreas Weigert Dominique Thomas Julia Schmetzer Sandra Trautmann Marthe-Susanna Wegner Heinfried H. Radeke Natalie Filmann Bernhard Brüne Gerd Geisslinger Irmgard Tegeder Sabine Grösch 《Cellular and molecular life sciences : CMLS》2017,74(16):3039-3055
Loss of intestinal barrier functions is a hallmark of inflammatory bowel disease like ulcerative colitis. The molecular mechanisms are not well understood, but likely involve dysregulation of membrane composition, fluidity, and permeability, which are all essentially regulated by sphingolipids, including ceramides of different chain length and saturation. Here, we used a loss-of-function model (CerS2+/+ and CerS2?/? mice) to investigate the impact of ceramide synthase 2, a key enzyme in the generation of very long-chain ceramides, in the dextran sodium salt (DSS) evoked model of UC. CerS2?/? mice developed more severe disease than CerS2+/+ mice in acute DSS and chronic AOM/DSS colitis. Deletion of CerS2 strongly reduced very long-chain ceramides (Cer24:0, 24:1) but concomitantly increased long-chain ceramides and sphinganine in plasma and colon tissue. In naive CerS2?/? mice, the expression of tight junction proteins including ZO-1 was almost completely lost in the colon epithelium, leading to increased membrane permeability. This could also be observed in vitro in CerS2 depleted Caco-2 cells. The increase in membrane permeability in CerS2?/? mice did not manifest with apparent clinical symptoms in naive mice, but with slight inflammatory signs such as an increase in monocytes and IL-10. AOM/DSS and DSS treatment alone led to a further deterioration of membrane integrity and to severe clinical symptoms of the disease. This was associated with stronger upregulation of cytokines in CerS2?/? mice and increased infiltration of the colon wall by immune cells, particularly monocytes, CD4+ and Th17+ T-cells, and an increase in tumor burden. In conclusion, CerS2 is crucial for the maintenance of colon barrier function and epithelial integrity. CerS2 knockdown, and associated changes in several sphingolipids such as a drop in very long-chain ceramides/(dh)-ceramides, an increase in long-chain ceramides/(dh)-ceramides, and sphinganine in the colon, may weaken endogenous defense against the endogenous microbiome. 相似文献
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Seogang Hyun 《Cellular and molecular life sciences : CMLS》2013,70(13):2351-2365
How animals achieve their specific body size is a fundamental, but still largely unresolved, biological question. Over the past decades, studies on the insect model system have provided some important insights into the process of body size determination and highlighted the importance of insulin/insulin-like growth factor signaling. Fat body, the Drosophila counterpart of liver and adipose tissue, senses nutrient availability and controls larval growth rate by modulating peripheral insulin signaling. Similarly, insulin-like growth factor I produced from liver and muscle promotes postnatal body growth in mammals. Organismal growth is tightly coupled with the process of sexual maturation wherein the sex steroid hormone attenuates body growth. This review summarizes some important findings from Drosophila and mammalian studies that shed light on the general mechanism of animal size determination. 相似文献
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Sangeeta Chauhan Xinde Zheng Yue Ying Tan Boon-Hui Tay Shuhui Lim Byrappa Venkatesh Philipp Kaldis 《Cellular and molecular life sciences : CMLS》2012,69(22):3835-3850
Successful completion of the cell cycle relies on the precise activation and inactivation of cyclin-dependent kinases (Cdks) whose activity is mainly regulated by binding to cyclins. Recently, a new family of Cdk regulators termed Speedy/RINGO has been discovered, which can bind and activate Cdks but shares no apparent amino acid sequence homology with cyclins. All Speedy proteins share a conserved domain of approximately 140 amino acids called “Speedy Box”, which is essential for Cdk binding. Speedy/RINGO proteins display an important role in oocyte maturation in Xenopus. Interestingly, a common feature of all Speedy genes is their predominant expression in testis suggesting that meiotic functions may be the most important physiological feature of Speedy genes. Speedy homologs have been reported in mammals and can be traced back to the most primitive clade of chordates (Ciona intestinalis). Here, we investigated the evolution of the Speedy genes and have identified a number of new Speedy/RINGO proteins. Through extensive analysis of numerous species, we discovered diverse evolutionary histories: the number of Speedy genes varies considerably among species, with evidence of substantial gains and losses. Despite the interspecies variation, Speedy is conserved among most species examined. Our results provide a complete picture of the Speedy gene family and its evolution. 相似文献