The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila

Chen, Hsi‐Ju; Li, Qi; Nirala, Niraj K.; Ip, Y. Tony

doi:10.1016/j.stemcr.2020.03.021

Cited by 20 publications

(28 citation statements)

References 65 publications

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“…The knockdown of hoka in the adult midgut leads to a shortened lifespan in adult flies, intestinal barrier dysfunction, increased ISC proliferation, and the accumulation of ECs. These results are consistent with the recent observation for ssk , mesh , and Tsp2A -RNAi in the adult midgut (Salazar et al, 2018; Xu et al, 2019; Izumi et al, 2019; Chen et al, 2020). However, the defects observed in the hoka -RNAi midgut were less severe than in flies with RNAi for other sSJ-proteins (Izumi et al, 2019).…”

Section: Discussionsupporting

confidence: 93%

“…Recently, we and other groups reported that the knockdown of ssk , mesh , or Tsp2A in adult ECs led to a remarkably shortened lifespan in adult flies, increased ISC proliferation, and intestinal hypertrophy, accompanied by the accumulation of ECs in the midgut (Salazar et al, 2018; Xu et al, 2019; Izumi et al, 2019; Chen et al, 2020). Therefore, we investigated whether the knockdown of hoka from adult ECs also caused similar phenotypes as observed with the knockdown of other sSJ-proteins.…”

Section: Resultsmentioning

confidence: 96%

“…The identification of Ssk, Mesh, and Tsp2A has provided an experimental system to analyze the role of sSJs in the Drosophila midgut (Furuse and Izumi, 2017). Recent studies have shown that sSJs regulate the epithelial barrier function and also ISC proliferation and EC behavior in the midgut (Salazar et al, 2018; Xu et al, 2019; Izumi et al, 2019; Chen et al, 2020). Furthermore, sSJs are involved in epithelial morphogenesis, fluid transport, and macromolecule permeability in the Malpighian tubules (Jonusaite et al, 2020; Beyenbach et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…To maintain midgut homeostasis, ECs and EEs are continuously renewed by proliferation and differentiation of the ISC lineage through the production of intermediate differentiating cells, EBs and EMCs. Recently, we and other groups reported that the knockdown of sSJ-proteins Ssk, Mesh, and Tsp2A in the midgut causes intestinal hypertrophy accompanied by the overproliferation of ECs and ISC (Salazar et al, 2018; Xu et al, 2019; Izumi et al, 2019, Chen et al, 2020). These results indicate that sSJs play a crucial role in maintaining tissue homeostasis through the regulation of stem cell proliferation and enterocyte behavior in the Drosophila adult midgut.…”

Section: Introductionmentioning

confidence: 97%

“…In the Drosophila midgut, inhibition of the Hippo signaling pathway activates the transcriptional co-activator Yorkie (Yki), which results in accelerated ISC proliferation via the Unpaired (Upd)-Jak-Stat signaling pathway (Karpowicz et al, 2010; Ren et al, 2010; Shaw et al, 2010). Recent studies have shown that Yki is involved in ISC overproliferation caused by the depletion of sSJ-proteins in the midgut (Xu et al, 2019; Chen et al, 2020). Furthermore, Xu et al (2019) have shown that aPKC is activated in the Tsp2A -RNAi treated midgut, leading to activation of its downstream target Yki and causing ISC overproliferation through the activation of the Upd-JAK-Stat signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

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A novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in theDrosophilagut

Izumi

Furuse

2020

Preprint

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Smooth septate junctions (sSJs) regulate the paracellular transport in the intestinal and renal system in arthropods. In Drosophila, the organization and physiological function of sSJs are regulated by at least three sSJ-specific membrane proteins: Ssk, Mesh, and Tsp2A. Here, we report a novel sSJ membrane protein Hoka, which has a single membrane-spanning segment with a short extracellular region having 13-amino acids, and a cytoplasmic region with three repeats of the Tyr-Thr-Pro-Ala motif. The larval midgut in hoka-mutants shows a defect in sSJ structure. Hoka forms a complex with Ssk, Mesh, and Tsp2A and is required for the correct localization of these proteins to sSJs. Knockdown of hoka in the adult midgut leads to intestinal barrier dysfunction, stem cell overproliferation, and epithelial tumors. In hoka-knockdown midguts, aPKC is up-regulated in the cytoplasm and the apical membrane of epithelial cells. The depletion of aPKC and yki in hoka-knockdown midguts results in reduced stem cell overproliferation. These findings indicate that Hoka cooperates with the sSJ-proteins Ssk, Mesh, and Tsp2A to organize sSJs, and is required for maintaining intestinal stem cell homeostasis through the regulation of aPKC and Yki activities in the Drosophila midgut.Summary statementDepletion of hoka, a gene encoding a novel septate junction protein, from the Drosophila midgut results in the disruption of septate junctions, intestinal barrier dysfunction, stem cell overproliferation, and epithelial tumors.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in theDrosophilagut

Izumi

Furuse

2020

Preprint

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Requirement of Snakeskin for normal functions of midgut and Malpighian tubules in Henosepilachna vigintioctopunctata

Zhang

Yang

Jin

et al. 2023

Arch Insect Biochem Physiol

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Septate junctions (SJs) are located between epithelial cells and play crucial roles in epithelial barrier formation and epithelia cell homeostasis. Nevertheless, the molecular constituents, especially those related to smooth SJs (sSJs), have not been well explored in non‐Drosophilid insects. A putative integral membrane protein Snakeskin (Ssk) was identified in a Coleoptera foliar pest Henosepilachna vigintioctopunctata. RNA interference‐aided knockdown of Hvssk at the third‐instar larval stage arrested larval development. Most resultant larvae failed to shed larval exuviae until their death. Silence of Hvssk at the fourth‐instar larvae inhibited the growth and reduced foliage consumption. Dissection and microscopic observation revealed that compromised expression of Hvssk caused obvious phenotypic defects in the midgut. A great number of morphologically abnormal columnar epithelial cells accumulated throughout the midgut lumen. Moreover, numerous vesicles were observed in the malformed cells of the Malpighian tubules (Mt). All the Hvssk depleted larvae remained as prepupae; they gradually darkened and eventually died. Furthermore, depletion of Hvssk at the pupal stage suppressed adult feeding and shortened adult lifespan. These findings demonstrated that Ssk plays a vital role in the integrity and function of both midguts and Mt, and established the conservative roles of Ssk in the formation of epithelial barrier and the homeostasis of epithelial cells in H. vigintioctopunctata.

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The gut commensal bacterium Enterococcus faecalis LX10 contributes to defending against Nosema bombycis infection in Bombyx mori

Zhang

Feng

et al. 2022

Pest Management Science

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BACKGROUND: Microsporidia, a group of obligate intracellular fungal-related parasites, have been used as efficient biocontrol agents for agriculture and forestry pests due to their host specificity and transovarial transmission. They mainly infect insect pests through the intestinal tract, but the interactions between microsporidia and the gut microbiota of the host have not been well demonstrated.RESULTS: Based on the microsporidia-Bombyx mori model, we report that the susceptibility of silkworms to exposure to the microsporidium Nosema bombycis was both dose and time dependent. Comparative analyses of the silkworm gut microbiome revealed substantially increased abundance of Enterococcus belonging to Firmicutes after N. bombycis infection. Furthermore, a bacterial strain (LX10) was obtained from the gut of B. mori and identified as Enterococcus faecalis based on 16S rRNA sequence analysis. E. faecalis LX10 reduced the N. bombycis spore germination rate and the infection efficiency in vitro and in vivo, as confirmed by bioassay tests and histopathological analyses. In addition, after simultaneous oral feeding with E. faecalis LX10 and N. bombycis, gene (Akirin, Cecropin A, Mesh, Ssk, DUOX and NOS) expression, hydrogen peroxide and nitric oxide levels, and glutathione S-transferase (GST) activity showed different degrees of recovery and correction compared with those under N. bombycis infection alone. Finally, the enterococcin LX protein was identified from sterile LX10 fermentation liquid based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.CONCLUSION: Altogether, the results revealed that E. faecalis LX10 with anti-N. bombycis activity might play an important role in protecting silkworms from microsporidia. Removal of these specific commensal bacteria with antibiotics and utilization of transgenic symbiotic systems may effectively improve the biocontrol value of microsporidia.

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The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila

Cited by 20 publications

References 65 publications

A novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in theDrosophilagut

A novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in theDrosophilagut

Requirement of Snakeskin for normal functions of midgut and Malpighian tubules in Henosepilachna vigintioctopunctata

The gut commensal bacterium Enterococcus faecalis LX10 contributes to defending against Nosema bombycis infection in Bombyx mori

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