scholarly journals The novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in the Drosophila gut

2021 ◽  
Vol 134 (6) ◽  
Author(s):  
Yasushi Izumi ◽  
Kyoko Furuse ◽  
Mikio Furuse
Keyword(s):  
Stem Cell ◽  
Membrane Protein ◽  
Intestinal Barrier ◽  
Septate Junction ◽  
The Novel ◽  
Barrier Dysfunction ◽  
Cell Homeostasis ◽  
Extracellular Region ◽  
Membrane Spanning ◽  
Specific Membrane

ABSTRACT Smooth septate junctions (sSJs) regulate the paracellular transport in the intestinal tract 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, and a cytoplasmic region with Tyr-Thr-Pro-Ala motifs. 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 and stem cell overproliferation. In hoka-knockdown midguts, aPKC is upregulated 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.

scholarly journals A novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in the Drosophila gut

2020 ◽  
Author(s):  
Yasushi Izumi ◽  
Kyoko Furuse ◽  
Mikio Furuse
Keyword(s):  
Stem Cell ◽  
Membrane Protein ◽  
Intestinal Barrier ◽  
Septate Junction ◽  
Barrier Dysfunction ◽  
Septate Junctions ◽  
Cell Homeostasis ◽  
Intestinal Barrier Dysfunction ◽  
Epithelial Tumors ◽  
Junction Protein

AbstractSmooth 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.

scholarly journals Septate junctions regulate gut homeostasis through regulation of stem cell proliferation and enterocyte behavior in Drosophila

2019 ◽  
Author(s):  
Yasushi Izumi ◽  
Kyoko Furuse ◽  
Mikio Furuse
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Intestinal Barrier ◽  
Septate Junction ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Septate Junctions ◽  
Stem Cell Proliferation ◽  
Associated Proteins ◽  
Intestinal Hypertrophy

AbstractSmooth septate junctions (sSJs) contribute to the epithelial barrier, which restricts leakage of solutes through the paracellular route of epithelial cells in the Drosophila midgut. We previously identified three sSJ-associated membrane proteins, Ssk, Mesh, and Tsp2A, and showed that these proteins were required for sSJ formation and intestinal barrier function in the larval midgut. Here, we investigated the roles of sSJs in the Drosophila adult midgut. Depletion of any of the sSJ-proteins from enterocytes resulted in remarkably shortened lifespan and intestinal barrier dysfunction in flies. Interestingly, the sSJ protein-deficient flies showed intestinal hypertrophy accompanied by accumulation of morphologically abnormal enterocytes. The phenotype was associated with increased stem cell proliferation and activation of the MAP kinase and Jak-Stat pathways in stem cells. Loss of cytokines Unpaired2 and Unpaired3, which are involved in Jak-Stat pathway activation, suppressed the intestinal hypertrophy, but not the increased stem cell proliferation, in flies lacking Mesh. The present findings suggest that SJs play a crucial role in maintaining tissue homeostasis through regulation of stem cell proliferation and enterocyte behavior in the Drosophila adult midgut.Summary statementDepletion of smooth septate junction-associated proteins from enterocytes in the Drosophila adult midgut results in intestinal hypertrophy accompanied by accumulation of morphologically aberrant enterocytes and increased stem cell proliferation.

scholarly journals A Novel Membrane Protein-Specific Serine/Threonine Kinase: Tissue Distribution and Role in Sperm Maturation

ISRN Urology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7
Author(s):  
Debjani Nath ◽  
Arpita Bhoumik ◽  
Sujoy Das ◽  
Debdas Bhattacharyya ◽  
Sandhya R. Dungdung ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Membrane Protein ◽  
The Novel ◽  
Serine Threonine Kinase ◽  
Membrane Biology ◽  
Threonine Kinase ◽  
Apparent Homogeneity ◽  
Sperm Membrane ◽  
First Time ◽  
Specific Membrane

Our recent studies have described for the first time the purification of an ectoprotein kinase to apparent homogeneity using caprine sperm as the model. Purified ectokinase (CIK) is a novel membrane protein-specific kinase that phosphorylates serine and threonine residues of ectophosphoproteins. This study, using ELISA based on ecto-CIK antibody demonstrates that ecto-CIK level is remarkably higher in the sperm membrane than in the cytosol. The epididymal sperm maturational event as well as sperm vertical velocity is associated with a significant increase in the ecto-CIK level. Ecto-CIK, the membrane protein-specific kinase, is also present in all the tissues tested and is predominantly localized in the cell membrane. Ubiquitous localization of the novel kinase on the mammalian cell membrane suggests that the kinase may play pivotal role in gamete as well as somatic cell regulation by modulating membrane biology through serine/threonine phosphorylation of specific membrane proteins located in the ectodomains.

Abstract 40: Discovery and Characterization of the Novel Muscle-Specific Membrane Protein Smco1

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
James B Papizan ◽  
John R McAnally ◽  
Rhonda Bassel-Duby ◽  
Eric N Olson
Keyword(s):  
Skeletal Muscle ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Striated Muscle ◽  
Coiled Coil ◽  
Postnatal Growth ◽  
The Novel ◽  
And Function ◽  
Specific Membrane

Mutations in numerous membrane proteins cause debilitating myopathies. The discovery of novel muscle-specific, membrane proteins would likely provide insight into mechanisms of disease and potentially yield new therapeutic targets. Through bioinformatics screening for muscle-specific membrane proteins with unknown function, we identified C3orf43 or single-pass membrane protein with coiled-coil domains 1 (Smco1). Consistent with bioinformatics predictions, Smco1 is expressed exclusively in cardiac and skeletal muscle. We demonstrate with chromatin immunoprecipitation and luciferase promoter assays that Smco1 is a Mef2-regulated gene with robust expression occurring shortly after birth. Immunofluorescent analysis demonstrates Scmo1 localizes to the cardiomyocyte sarcolemma and intercalated disks. Talen-mediated disruption of Smco1 in mice results in stunted postnatal growth, cardiac hypoplasia and skeletal muscle myopathy as early as postnatal day 15. While studies are on going to determine the function of Smco1, our findings reveal an essential role of Smco1 in striated muscle structure and function. The identification of heart- and muscle-specific membrane proteins will likely illuminate the mechanisms of muscular membrane diseases.

scholarly journals BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Runze Quan ◽  
Chaoyue Chen ◽  
Wei Yan ◽  
Ying Zhang ◽  
Xi Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Survival Rates ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Protein Levels ◽  
Lps Challenge ◽  
Endotoxemia Model

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.

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