Papers by Bernard Charroux
Biology of the Cell, 1995
PLOS ONE, Feb 28, 2011
Toll and Toll-like receptors represent families of receptors involved in mediating innate immunit... more Toll and Toll-like receptors represent families of receptors involved in mediating innate immunity response in insects and mammals. Although Drosophila proteome contains multiple Toll paralogs, Toll-1 is, so far, the only receptor to which an immune role has been attributed. In contrast, every single mammalian TLR is a key membrane receptor upstream of the vertebrate immune signaling cascades. The prevailing view is that TLR-mediated immunity is ancient. Structural analysis reveals that Drosophila Toll-9 is the most closely related to vertebrate TLRs and utilizes similar signaling components as Toll-1. This suggests that Toll-9 could be an ancestor of TLR-like receptors and could have immune function. Consistently, it has been reported that over-expression of Toll-9 in immune tissues is sufficient to induce the expression of some antimicrobial peptides in flies. These results have led to the idea that Toll-9 could be a constitutively active receptor that maintain significant levels of antimicrobial molecules and therefore provide constant basal protection against microorganisms. To test theses hypotheses, we generated and analyzed phenotypes associated with a complete loss-of-function allele of Toll-9. Our results suggest that Toll-9 is neither required to maintain a basal anti-microbial response nor to mount an efficient immune response to bacterial infection.
Journal of Biological Chemistry, Aug 1, 2000
Spinal muscular atrophy is a common often lethal neurodegenerative disease resulting from deletio... more Spinal muscular atrophy is a common often lethal neurodegenerative disease resulting from deletions or mutations in the survival motor neuron gene (SMN). SMN is ubiquitously expressed in metazoan cells and plays a role in small nuclear ribonucleoprotein assembly and pre-mRNA splicing. Here we characterize the Schizosacharomyces pombe orthologue of SMN (yeast SMN (ySMN)). We report that the ySMN protein is essential for viability and localizes in both the cytoplasm and the nucleus. Like human SMN, we show that ySMN can oligomerize. Remarkably, ySMN interacts directly with human SMN and Sm proteins. The highly conserved carboxyl-terminal domain of ySMN is necessary for the evolutionarily conserved interactions of SMN and required for cell viability. We also demonstrate that the conserved amino-terminal region of ySMN is not required for SMN and Sm binding but is critical for the housekeeping function of SMN.
Current Biology, Jul 1, 2001
that plays a role in snRNP assembly, pre-mRNA splicing, and transcription. The functions of SMN i... more that plays a role in snRNP assembly, pre-mRNA splicing, and transcription. The functions of SMN in these processes are mediated by a direct interaction
Journal of Neurogenetics, 2010
Seminars in Immunology, Feb 1, 2012
Millions of people suffer from inflammatory diseases of the intestine, some of them potentiating ... more Millions of people suffer from inflammatory diseases of the intestine, some of them potentiating gastrointestinal cancer. These gut-associated pathologies arise from imbalanced interactions between the host gut epithelia and resident or ingested microbes, interactions that are still poorly understood at the molecular level. Drosophila has been a very powerful model to study development and diseases. Its relatively simple tissue organization and sophisticated genetics are some of the advantages of using it as an experimental model to dissect gut-microbe interactions. Recent progress made in various research fields such as Drosophila microbiota composition, gut epithelium structure or gut immune reactions led us to believe that Drosophila is becoming an ad hoc model system to dissect the mechanisms that cooperate to maintain intestinal homeostasis in higher eukaryotes. It further may help us understand how an alteration of these finely tuned processes precipitates the inflammatory processes found in some inflammatory bowel diseases.
Biology Open, Dec 6, 2013
Sorting of secretory cargo and retrieval of components of the biosynthetic pathway occur in organ... more Sorting of secretory cargo and retrieval of components of the biosynthetic pathway occur in organelles such as the Golgi apparatus, the endoplasmic reticulum and the endosomes. In order to perform their functions in protein sorting, these organelles require a weakly acidified lumen. In vitro data have shown that Golgi luminal pH is in part regulated by an anion channel called Golgi pH Regulator (GPHR). Mammalian cells carrying a mutated GPHR version present an increased luminal pH leading to delayed protein transport, impaired glycosylation and Golgi disorganization. Using Drosophila as a model system, we present here the first phenotypic consequences, at the organism level, of a complete lack of GPHR function. We show that, although all individuals carrying complete loss-of-function mutations in the dGPHR gene can go through embryonic development, most of them die at late larval stages. The dGPHR mutations are, however, sublethal and can therefore generate escapers that are smaller than controls. Using cellular and molecular readouts, we demonstrate that the effects of dGPHR mutation on larval growth are not due to Insulin signaling pathway impairment and can be rescued by providing dGPHR in only some of the larval tissues. We reveal that, although functionally exchangeable, the invertebrate and vertebrate GPHRs display not completely overlapping sub-cellular localization. Whereas the mammalian GPHR is a Golgi-only associated protein whose inactivation disturbs the Golgi apparatus, our data suggest that dGPHR is expressed in both the ER and the Golgi and that dGPHR mutant flies have defects in both organelles that lead to a defective secretory pathway.
Developmental Biology, Mar 1, 2006
Dentato-rubral and pallido-luysian atrophy (DRPLA) is a dominant, progressive neurodegenerative d... more Dentato-rubral and pallido-luysian atrophy (DRPLA) is a dominant, progressive neurodegenerative disease caused by the expansion of polyglutamine repeats within the human Atrophin-1 protein. Drosophila Atrophin and its human orthologue are thought to function as transcriptional co-repressors. Here, we report that Drosophila Atrophin participates in the negative regulation of Epidermal Growth Factor Receptor (EGFR) signaling both in the wing and the eye imaginal discs. In the wing pouch, Atrophin loss of function clones induces cell autonomous expression of the EGFR target gene Delta, and the formation of extra vein tissue, while overexpression of Atrophin inhibits EGFRdependent vein formation. In the eye, Atrophin cooperates with other negative regulators of the EGFR signaling to prevent the differentiation of surplus photoreceptor cells and to repress Delta expression. Overexpression of Atrophin in the eye reduces the EGFR-dependent recruitment of cone cells. In both the eye and wing, epistasis tests show that Atrophin acts downstream or in parallel to the MAP kinase rolled to modulate EGFR signaling outputs. We show that Atrophin genetically cooperates with the nuclear repressor Yan to inhibit the EGFR signaling activity. Finally, we have found that expression of pathogenic or normal forms of human Atrophin-1 in the wing promotes wing vein differentiation and acts as dominant negative proteins inhibiting endogenous fly Atrophin activity.
Molecular and Cellular Biology, Nov 1, 1999
We have characterized the Drosophila bancal gene, which encodes a Drosophila homologue of the ver... more We have characterized the Drosophila bancal gene, which encodes a Drosophila homologue of the vertebrate hnRNP K protein. The bancal gene is essential for the correct size of adult appendages. Reduction of appendage size in bancal mutant flies appears to be due mainly to a reduction in the number of cell divisions in the imaginal discs. Transgenes expressing Drosophila or human hnRNP K are able to rescue weak bancal phenotype, showing the functional similarity of these proteins in vivo. High levels of either human or Drosophila hnRNP K protein in imaginal discs induces programmed cell death. Expression of the antiapoptotic P35 protein suppresses this phenotype in the eye, suggesting that apoptosis is the major cellular defect caused by overexpression of K protein. Finally, the human K protein acts as a negative regulator of bancal gene expression. We propose that negative autoregulation limits the level of Bancal protein produced in vivo.
Proceedings of the National Academy of Sciences of the United States of America, Jun 16, 2009
PLOS Genetics, Jan 13, 2017
Behavior evolution can promote the emergence of agricultural pests via ecological niche changes. ... more Behavior evolution can promote the emergence of agricultural pests via ecological niche changes. The underlying neuronal mechanisms are poorly understood. We investigate the chemosensory changes underlying the evolutionary shift of oviposition substrate of the pest Drosophila suzukii from rotten to ripe fruits. Using a model substrate for fermented fruits and genetic manipulations, we show that an increase in valuation of fruit sugars during oviposition decisions drives D. suzukii to oviposit on ripe fruits as opposed to the model D. melanogaster which prefers rotten fruits. Inter-species comparative in vivo calcium imaging of sugar Gustatory Receptor Neurons suggests that increased sugar valuation in D. suzukii is related to neuronal sensitivity changes at multiple levels of the oviposition circuitry. Our results show that the tuning of sugar valuation has contributed to the evolution of oviposition preference on ripe fruit of D. suzukii.
Journal of Cell Biology, Mar 20, 2000
The survival of motor neurons (SMN) protein, the product of the neurodegenerative disease spinal ... more The survival of motor neurons (SMN) protein, the product of the neurodegenerative disease spinal muscular atrophy (SMA) gene, is localized both in the cytoplasm and in discrete nuclear bodies called gems. In both compartments SMN is part of a large complex that contains several proteins including Gemin2 (formerly SIP1) and the DEAD box protein Gemin3. In the cytoplasm, the SMN complex is associated with snRNP Sm core proteins and plays a critical role in spliceosomal snRNP assembly. In the nucleus, SMN is required for pre-mRNA splicing by serving in the regeneration of spliceosomes. These functions are likely impaired in cells of SMA patients because they have reduced levels of functional SMN. Here, we report the identification by nanoelectrospray mass spectrometry of a novel component of the SMN complex that we name Gemin4. Gemin4 is associated in vivo with the SMN complex through a direct interaction with Gemin3. The tight interaction of Gemin4 with Gemin3 suggests that it could serve as a cofactor of this DEAD box protein. Gemin4 also interacts directly with several of the Sm core proteins. Monoclonal antibodies against Gemin4 efficiently immunoprecipitate the spliceosomal U snRNAs U1 and U5 from Xenopus oocytes cytoplasm. Immunolocalization experiments show that Gemin4 is colocalized with SMN in the cytoplasm and in gems. Interestingly, Gemin4 is also detected in the nucleoli, suggesting that the SMN complex may also function in preribosomal RNA processing or ribosome assembly.
<p>(A) Dorsal views of third instar larvae and pupal cases showing ectopic expression of &l... more <p>(A) Dorsal views of third instar larvae and pupal cases showing ectopic expression of <i>Diap1-GFP4</i>.<i>3</i> in <i>PGRP-LF</i> mutant LECs, trachea and hindguts. See also <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006569#pgen.1006569.s007" target="_blank">S7 Fig</a>. (B) Expression of <i>Diap1</i> mRNA is higher in hindgut, trachea and cuticle from <i>PGRP-LF</i> mutant larvae than from controls. (C) <i>Diap1-GFP4</i>.<i>3</i> expression is induced in cells overexpressing IMD. Dorsal epidermis (top images) and fat body (bottom images) of <i>en</i><sup><i>Gal4</i></sup>, <i>UAS-RFP</i>/+ (control) and <i>en</i><sup><i>Gal4</i></sup>, <i>UAS-RFP</i>/+; <i>UAS-IMD</i>/+ (<i>UAS-IMD</i>) larvae are shown. In LECs and fat body cells, IMD expression induce <i>Diap1-GFP4</i>.<i>3</i> cell autonomously (arrows). (D) Expression of <i>Diap1</i> mRNA is induced following overexpression of <i>IMD</i> and <i>PGRP-LCa</i> in adult fat body. Abdomen from 6d old females of the following genotypes were dissected and analyzed by q-RT-PCR: <i>Cg</i><sup><i>Gal4</i></sup><i>/nlsUAS-GFP</i> (control), <i>Cg</i><sup><i>Gal4</i></sup>/+<i>; UAS-IMD</i>/+ (<i>UAS-IMD</i>) and <i>Cg</i><sup><i>Gal4</i></sup>/+<i>; UAS-PGRP-LCa</i>/+ (UAS-PGRP-LCa). For (B) and (D) mRNA level in control was set to 1, and values obtained with tissues or larvae of indicated genotypes were expressed as a fold of this value. For (B) and (D) histograms correspond to the mean value ± SD of three independent experiments. Values indicated by symbols (*) are statistically significant (t-test, p < 0.05). ns: not significantly different.</p
Reference Module in Neuroscience and Biobehavioral Psychology, 2017
Dentatorubral-pallidoluysian atrophy is a polyglutamine disorder caused by expansion of a CAG rep... more Dentatorubral-pallidoluysian atrophy is a polyglutamine disorder caused by expansion of a CAG repeat tract within the human atrophin 1 gene. Truncated fragments of polyQ Atrophin one accumulate in neuronal nuclei of DRPLA patients and represent the toxic form. The normal Atrophin 1 protein is conserved from Drosophila to mammals where it acts as transcriptional co-repressor.
Abstract. The survival of motor neurons (SMN) protein, the product of the neurodegenerative disea... more Abstract. The survival of motor neurons (SMN) protein, the product of the neurodegenerative disease spinal muscular atrophy (SMA) gene, is localized both in the cytoplasm and in discrete nuclear bodies called gems. In both compartments SMN is part of a large complex that contains several proteins including Gemin2 (formerly SIP1) and the DEAD box protein Gemin3. In the cytoplasm, the SMN complex is associated with snRNP Sm core proteins and plays a critical role in spliceosomal snRNP assembly. In the nucleus, SMN is required for pre-mRNA splicing by serving in the regeneration of spliceosomes. These functions are likely impaired in cells of SMA patients because they have reduced levels of functional SMN. Here, we report the identification by nanoelectrospray mass spectrometry of a novel component of the SMN complex that we name Gemin4. Gemin4 is associated in vivo with the
bioRxiv, 2021
Bacteria that colonize eukaryotic gut have profound influences on the physiology of their host. I... more Bacteria that colonize eukaryotic gut have profound influences on the physiology of their host. In Drosophila, many of these effects are mediated by the adipocytes that combine immune and metabolic functions. We show here that gut colonization by specific bacteria species stimulate lipogenesis in surrounding enterocytes but also in remote fat body cells and ovaries. This bacteria-dependent lipid production is mediated by SREBP and requires a functional insulin signaling. However, it is antagonized by microbiota-born peptidoglycan which by activating NF-κB signaling, cell-autonomously represses SREPP activation in adipocytes but not in enterocytes. We finally show that by reducing microbiota-derived PGN, the gut-produced PGRP-LB amidase balances host immune and metabolic responses of the fat body to gut-associated bacteria. In the absence of such modulation, uncontrolled immune pathway activation prevents lipid production by the fat body resulting in infection-dependent host death. B...
eLife, Jan 7, 2017
As infectious diseases pose a threat to host integrity, eukaryotes have evolved mechanisms to eli... more As infectious diseases pose a threat to host integrity, eukaryotes have evolved mechanisms to eliminate pathogens. In addition to develop strategies reducing infection, animals can engage in behaviors that lower the impact of the infection. The molecular mechanisms by which microbes impact host behavior are not well understood. We demonstrate that bacterial infection of Drosophila females reduces oviposition and that peptidoglycan, the component that activates Drosophila antibacterial response, is also the elicitor of this behavioral change. We show that peptidoglycan regulates egg-laying rate by activating NF-κB signaling pathway in octopaminergic neurons and that, a dedicated peptidoglycan degrading enzyme acts in these neurons to buffer this behavioral response. This study shows that a unique ligand and signaling cascade are used in immune cells to mount an immune response and in neurons to control fly behavior following infection. This may represent a case of behavioral immunity.
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Papers by Bernard Charroux