<i>Macroglobulin complement-related</i>encodes a protein required for septate junction organization and paracellular barrier function in<i>Drosophila</i>

Hall, Sonia; Bone, Courtney R.; Oshima, Kenzi; Zhang, Liang; McGraw, Molly; Lucas, Bethany; Fehon, Richard G.; Ward, Robert E.

doi:10.1242/dev.102152

Cited by 40 publications

(61 citation statements)

References 45 publications

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“…The strong upregulation of the different Teps (especially Tep2) in the salivary glands in the presence of the trypanosome infection suggests a possible role of this protein family in the interaction with the Tbb parasite population in the tissue. Moreover, the high similarity of the predicted Tep4 protein with the DmTep6-Mcr protein in Drosophila could indicate a similar role of this protein as described for Drosophila in the formation and maintenance of the septate junctions in the epithelial cell lining in the tsetse salivary glands [37, 38]. Indeed, the tight attachment of the trypanosome flagellum to this epithelial lining [39] in the infected glands could possibly cause damage to the septate junctions.…”

Section: Resultsmentioning

confidence: 99%

“…So far, in Drosophila more than 20 genes have been described with a function in the establishment and maintenance of SJs (reviewed in [38]). We identified a series of transcripts encoding for SJs proteins as being upregulated in trypanosome-infected glands including cell adhesion molecules Contactin (GMOY007352), Neuroglian (GMOY008087), Neurexin IV (GMOY005058) and Lachesin (GMOY006705); a transmembrane protein sinuous (GMOY007768); a cytoplasmic protein coracle (GMOY009095) and crooked (GMOY003227) and coiled (GMOY010273) coding for proteins required for SJ assembly.…”

Section: Resultsmentioning

confidence: 99%

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Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland

2016

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BackgroundFor their transmission, African trypanosomes rely on their blood feeding insect vector, the tsetse fly (Glossina sp.). The ingested Trypanosoma brucei parasites have to overcome a series of barriers in the tsetse fly alimentary tract to finally develop into the infective metacyclic forms in the salivary glands that are transmitted to a mammalian host by the tsetse bite. The parasite population in the salivary gland is dense with a significant number of trypanosomes tightly attached to the epithelial cells. Our current knowledge on the impact of the infection on the salivary gland functioning is very limited. Therefore, this study aimed to gain a deeper insight into the global gene expression changes in the salivary glands of Glossina morsitans morsitans in response to an infection with the T. brucei parasite. A detailed whole transcriptome comparison of midgut-infected tsetse with and without a mature salivary gland infection was performed to study the impact of a trypanosome infection on different aspects of the salivary gland functioning and the mechanisms that are induced in this tissue to tolerate the infection i.e. to control the negative impact of the parasite presence. Moreover, a transcriptome comparison with age-matched uninfected flies was done to see whether gene expression in the salivary glands is already affected by a trypanosome infection in the tsetse midgut.ResultsBy a RNA-sequencing (RNA-seq) approach we compared the whole transcriptomes of flies with a T. brucei salivary gland/midgut infection versus flies with only a midgut infection or versus non-infected flies, all with the same age and feeding history. More than 7500 salivary gland transcripts were detected from which a core group of 1214 differentially expressed genes (768 up- and 446 down-regulated) were shared between the two transcriptional comparisons. Gene Ontology enrichment analysis and detailed gene expression comparisons showed a diverse impact at the gene transcript level. Increased expression was observed for transcripts encoding for proteins involved in immunity (like several genes of the Imd-signaling pathway, serine proteases, serpins and thioester-containing proteins), detoxification of reactive species, cell death, cytoskeleton organization, cell junction and repair. Decreased expression was observed for transcripts encoding the major secreted proteins such as 5′-nucleotidases, adenosine deaminases and the nucleic acid binding proteins Tsals. Moreover, expression of some gene categories in the salivary glands were found to be already affected by a trypanosome midgut infection, before the parasite reaches the salivary glands.ConclusionsThis study reveals that the T. brucei population in the tsetse salivary gland has a negative impact on its functioning and on the integrity of the gland epithelium. Our RNA-seq data suggest induction of a strong local tissue response in order to control the epithelial cell damage, the ROS intoxication of the cellular environment and the parasite infection, resulting in the fly tolera...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland

2016

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“…113,114 Mcr is also reported to function in hemocytic immune responses. Mcr is expressed in plasmatocytes.…”

Section: Epithelial and Cell-mediated Immune Responsesmentioning

confidence: 99%

Arthropod Innate Immune Systems and Vector-Borne Diseases

2017

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Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases, including malaria, sleeping sickness, Dengue, and Zika, yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is the group of genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins such as antimicrobial peptides, thioester-containing proteins, and transglutaminases effect responses such as lysis, phagocytosis, melanization, and agglutination. Effector responses are initiated by damage signals such as reactive oxygen species signaling from epithelial cells and recognized by cell surface receptors on hemocytes. Antiviral immunity is primarily mediated by siRNA pathways but coupled with interferon-like signaling, antimicrobial peptides, and thioester-containing proteins. Molecular mechanisms of immunity are closely linked to related traits of longevity and fertility, and arthropods have the capacity for innate immunological memory. Advances in understanding vector immunity can be leveraged to develop novel control strategies for reducing the rate of transmission of both ancient and emerging threats to global health.

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“…Primary antibodies were: mouse anti-Gli 1F6.3 at 1:200 (Auld et al, 1995), rabbit anti-Gli at 1:300 (Venema et al, 2004), mouse anti-Dlg 4F3 at 1:200 (Developmental Studies Hybridoma Bank) (Parnas et al, 2001), rat anti-DE-Cadherin at 1:50 (Developmental Studies Hybridoma Bank), mouse anti-Coracle (9C and C615-16B cocktail) at 1:100 (Developmental Studies Hybridoma Bank) (Fehon et al, 1994), rabbit anti-NrxIV at 1:500 (Baumgartner et al, 1996), guinea pig anti-Mcr at 1:800 (Hall et al, 2014), mouse anti-Fasciclin 3 at 1:100 (Developmental Studies Hybridoma Bank), rabbit anti-phosphorylated Mad at 1:200 (Cell Signaling). DAPI was used at 1:1000 (Thermo Scientific).…”

Section: Immunolabellingmentioning

confidence: 99%

“…Pleated septate junctions form a ladder-like array of electron-dense septa located just below the adherens junction (Tepass and Hartenstein, 1994). Septate junctions comprise an interdependent protein complex, including Neurexin IV (NrxIV) (Baumgartner et al, 1996), Coracle (Fehon et al, 1994), Na + /K + ATPase and Neuroglian (Genova and Fehon, 2003;Paul et al, 2003), Contactin (Faivre-Sarrailh et al, 2004) and Mcr (Batz et al, 2014;Hall et al, 2014). In many epithelia, a specialized junction, the tricellular junction (TCJ), forms at the convergence of the tight junctions or septate junctions from three cells to create a permeability barrier at the corners of neighbouring cells.…”

Section: Introductionmentioning

confidence: 99%

The Drosophila tricellular junction protein Gliotactin regulates its own mRNA levels through BMP-mediated induction of miR-184

Sharifkhodaei

Barmchi

Gilbert

et al. 2016

Journal of Cell Science

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Epithelial bicellular and tricellular junctions are essential for establishing and maintaining permeability barriers. Tricellular junctions are formed by the convergence of three bicellular junctions at the corners of neighbouring epithelia. Gliotactin, a member of the Neuroligin family, is located to the Drosophila tricellular junction and is critical for the formation of tricellular and septate junctions and permeability barrier function. Gliotactin protein levels are tightly controlled by tyrosine phosphorylation and endocytosis. Blocking endocytosis or overexpression of Gliotactin triggers spread away from the tricellular junction, resulting in apoptosis, delamination and migration of epithelial cells. We show that Gliotactin levels are also regulated at the mRNA level by microRNA-mediated degradation targeted to a short region in the 3'UTR that includes a conserved miR-184 target site. miR-184 also targets a suite of septate junction proteins including Neurexin-IV, coracle and Mcr. miR-184 expression is triggered when Gliotactin is overexpressed leading to activation of the BMP signaling pathway. Gliotactin specifically interferes with Dad, an inhibitory SMAD, leading to activation of the Tkv type-I receptor, and Mad to elevate the biogenesis and expression of miR-184.

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Macroglobulin complement-relatedencodes a protein required for septate junction organization and paracellular barrier function inDrosophila

Cited by 40 publications

References 45 publications

Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland

Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland

Arthropod Innate Immune Systems and Vector-Borne Diseases

The Drosophila tricellular junction protein Gliotactin regulates its own mRNA levels through BMP-mediated induction of miR-184

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