The endoplasmic reticulum (ER) is an organelle specialized for the folding and assembly of secretory transmembrane proteins. ER homeostasis often perturbed in tumor cells due to dramatic changes solid microenvironment, thereby leading activation adaptive mechanism named Unfolded Protein Response (UPR). UPR sensor IRE1α has been described play important role progression. However, molecular events associated with this phenotype remain poorly characterized. In present study, we examined effects...

We performed a review of public microarray data that revealed significant down-regulation Rnd3 expression in hepatocellular carcinoma (HCC), as compared to nontumor liver. Rnd3/RhoE is an atypical RhoGTPase family member because it always under its active GTP-bound conformation and not sensitive classical regulators. was validated by quantitative real-time polymerase chain reaction 120 independent tumors. Moreover, down-expression confirmed using immunohistochemistry on tumor sections...

The most common cystic fibrosis (CF) causing mutation, deletion of phenylalanine 508 (ΔF508 or Phe508del), results in functional expression defect the CF transmembrane conductance regulator (CFTR) at apical plasma membrane (PM) secretory epithelia, which is attributed to degradation misfolded channel endoplasmic reticulum (ER). Deletion 670 (ΔF670) yeast oligomycin resistance 1 gene (YOR1, an ABC transporter) Saccharomyces cerevisiae phenocopies ΔF508-CFTR folding and trafficking defects....

Approximately 50% of cystic fibrosis (CF) patients are heterozygous with a rare mutation on at least one allele. Several mutants exhibit functional defects, correctable by gating potentiators. Long-term exposure (≥24 h) to the only available potentiator drug, VX-770, leads biochemical and downregulation F508del-CFTR both in immortalized primary human airway cells, possibly other CF mutants, attenuating its beneficial effect. Based these considerations, we wanted determine effect chronic...

Microvillus inclusion disease (MVID) is a congenital intestinal malabsorption disorder caused by defective apical vesicular transport. Existing cellular models do not fully recapitulate this heterogeneous pathology. The aim of study was to characterize 3-dimensional organoids that continuously generate polarized absorptive cells as an accessible and relevant model investigate MVID.Intestinal from Munc18-2/Stxbp2-null mice are deficient for transport were subjected enterocyte-specific...

Intestine function relies on the strong polarity of intestinal epithelial cells and array microvilli forming a brush border at their luminal pole. Combining genetic RNAi screen in vivo super-resolution imaging C. elegans intestine, we uncovered that V0 sector V-ATPase (V0-ATPase) controls late apical trafficking step, involving RAB-11+ endosomes SNARE SNAP-29, necessary to maintain polarized localization both modules proteins. We show V0-ATPase pathway also genetically interacts with...

Spatiotemporal regulation of RhoGTPases such as RhoA is required at the cell leading edge to achieve migration. p190RhoGAP (p190A) main negative regulator and localizes membrane protrusions, where its GTPase-activating protein (GAP) activity for directional In this study, we investigated molecular processes responsible p190A targeting actin protrusions. By analyzing subcellular localization truncated versions in hepatocellular carcinoma cells, identified a novel functional domain: protrusion...

RhoGTPases are GDP/GTP molecular switches that control a wide variety of cellular processes, thereby contributing to many diseases, including cancer. As consequence, there is great interest in the identification small-molecule inhibitors RhoGTPases. In present paper, using property GTP-loaded bind their effectors, we describe miniaturized and robust assay monitor Rac1 GTPase activation suitable for large-scale high-throughput screening. A pilot compound library screen revealed topoisomerase...

ABSTRACT The intestinal brush border is made of an array microvilli that increases the membrane surface area for nutrient processing, absorption and host defense. Studies on mammalian cultured epithelial cells have uncovered some molecular players physical constraints required to establish this apical specialized membrane. However, building maintenance a in vivo has not yet been investigated detail. Here, we combined super-resolution imaging, transmission electron microscopy genome editing...

ABSTRACT Apical polarity of cystic fibrosis transmembrane conductance regulator (CFTR) is essential for solute and water transport in secretory epithelia can be impaired human diseases. Maintenance apical the face CFTR non-polarized delivery inefficient retention mutant CFTRs lacking PDZ-domain protein (NHERF1, also known as SLC9A3R1) interaction, remains enigmatic. Here, we show that basolateral originates from biosynthetic (∼35%) endocytic (∼65%) recycling missorting. Basolateral channels...

Abstract Intestine function relies on the strong polarity of intestinal epithelial cells and array microvilli forming a brush border at their luminal pole. Combining genetic RNAi screen in vivo super-resolution imaging C . elegans intestine, we uncovered that V0 sector V-ATPase (V0-ATPase) controls late apical trafficking step, involving RAB-11 endosomes SNARE SNAP-29, necessary to maintain polarized localization both modules proteins. We show V0-ATPase pathway also genetically interacts...

An array detector allows a resolution gain for confocal microscopy by combining images sensed set of photomultipliers tubes (or sub-detectors). Several methods have been proposed to reconstruct high-resolution image linearly sub-detector images, especially the fluorescence emission difference (FED) technique. To improve and contrast FED based on an detector, we propose associate sparse denoising with spatial adaptive estimation. We show both calibration slides real data that our approach...

Abstract Maintenance of the polarity epithelial cells facing lumen small intestine is crucial to ensure vectorial absorption nutrients as well integrity apical brush border and intestinal barrier. Polarized vesicular trafficking plays a key role in this process, defective transport due mutations trafficking-related genes has been shown affect nutrient absorption. Interestingly, it demonstrated that downregulation polarized sorting clathrin adaptor AP-1B led both proliferation defects mouse...

SUMMARY Apical polarity of cystic fibrosis transmembrane conductance regulator (CFTR) is essential for solute and water transport in secretory epithelia can be impaired human diseases. Maintenance apical the face CFTR non-polarized delivery compromised retention mutant CFTRs lacking PDZ-domain protein (NHERF1) interaction, remains enigmatic. Here we show that basolateral originates from biosynthetic (~35%) endocytic (~65%) recycling missorting. Basolateral channels are retrieved via...

Summary Intestinal microvillus atrophy is a major cause of enteropathies such as idiopathic or congenital diarrhea that are often associated with severe morbidity. It can be caused by genetic disorders, inflammatory diseases, toxins pathogens. In particular, Microvillus inclusion disease (MVID) characterized chronic intractable and atrophy. triggered mutations in MYO5B, STX3, MUNC18 . 2 UNC45A which alter epithelial polarity affecting apical trafficking intestinal cells. Furthermore, we...

Abstract The intestinal brush border is made of an array microvilli that increases the membrane surface area for nutrient processing, absorption, and host defence. Studies on mammalian cultured epithelial cells uncovered some molecular players physical constrains required to establish this apical specialized membrane. However, building maintenance a in vivo has not been investigated detail yet. Here, we combined super-resolution imaging, transmission electron microscopy genome editing...