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https://www.readbyqxmd.com/read/28724787/disrupted-apical-exocytosis-of-cargo-vesicles-causes-enteropathy-in-fhl5-patients-with-munc18-2-mutations
#1
Georg F Vogel, Jorik M van Rijn, Iris M Krainer, Andreas R Janecke, Carsten Posovzsky, Marta Cohen, Claire Searle, Prevost Jantchou, Johanna C Escher, Natalie Patey, Ernest Cutz, Thomas Müller, Sabine Middendorp, Michael W Hess, Lukas A Huber
Familial hemophagocytic lymphohistiocytosis 5 (FHL5) is an autosomal recessive disease caused by mutations in STXBP2, coding for Munc18-2, which is required for SNARE-mediated membrane fusion. FHL5 causes hematologic and gastrointestinal symptoms characterized by chronic enteropathy that is reminiscent of microvillus inclusion disease (MVID). However, the molecular pathophysiology of FHL5-associated diarrhea is poorly understood. Five FHL5 patients, including four previously unreported patients, were studied...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28596241/disruption-of-rab8a-and-rab11a-causes-formation-of-basolateral-microvilli-in-neonatal-enteropathy
#2
Qiang Feng, Edward M Bonder, Amy C Engevik, Lanjing Zhang, Matthew J Tyska, James R Goldenring, Nan Gao
Misplaced formation of microvilli to basolateral domains and intracellular inclusions in enterocytes are pathognomonic features in congenital enteropathy associated with STX3 mutation. While the demonstrated binding of Myo5b to the Rab8a and Rab11a small GTPases in vitro implicates cytoskeleton-dependent membrane sorting, the mechanisms underlying the microvillar location defect remain unclear. By selective or combinatory disruption of Rab8a and Rab11a membrane traffic in vivo, we demonstrate that transport of distinct cargo to the apical brush-border rely on either individual or both Rab regulators, whereas certain basolateral cargos are redundantly transported by both factors...
June 8, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28481180/trophoblast-glycoprotein-tpgb-5t4-in-human-placenta-expression-regulation-and-presence-in-extracellular-microvesicles-and-exosomes
#3
S M K Alam, S Jasti, S K Kshirsagar, D S Tannetta, R A Dragovic, C W Redman, I L Sargent, H C Hodes, T L Nauser, T Fortes, A M Filler, K Behan, D R Martin, T A Fields, B K Petroff, M G Petroff
BACKGROUND: Many parallels exist between growth and development of the placenta and that of cancer. One parallel is shared expression of antigens that may have functional importance and may be recognized by the immune system. Here, we characterize expression and regulation of one such antigen, Trophoblast glycoprotein (TPGB; also called 5T4), in the placenta across gestation, in placentas of preeclamptic (PE) pregnancies, and in purified microvesicles and exosomes. METHODS: Trophoblast glycoprotein expression was analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28478805/clostridium-butyricum-partially-regulates-the-development-of-colitis-associated-cancer-through-mir-200c
#4
Y Xiao, X Dai, K Li, G Gui, J Liu, H Yang
Colitis-associated cancer (CAC), one form of colorectal cancer (CRC),is an increasing concern worldwide. Both diagnosis and current therapy are challenging and bottlenecked. The aim of this study is to investigate novel mechanisms by which the therapeutic C. butyricum regulates colitis-induced oncogenesis. Mouse models of CAC were established with 2,4,6-Trinitrobenzenesulfonic acid (TNBS)and azoxymethane (AOM), following by biochemical, clinical and histological analysis. The integrity of epitheliumwas examined by electron microscopy (EM)...
April 29, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28431964/microvillus-specific-protein-tyrosine-phosphatase-sap-1-plays-a-role-in-regulating-the-intestinal-paracellular-transport-of-macromolecules
#5
Shingo Mori, Noriyasu Kamei, Yoji Murata, Kozo Takayama, Takashi Matozaki, Mariko Takeda-Morishita
The stomach cancer associated protein tyrosine phosphatase 1 (SAP-1) is a receptor-type protein tyrosine phosphatase that is specifically expressed on the apical membrane of the intestinal epithelium. SAP-1 is known to maintain the balance of phosphorylation of proteins together with protein kinases, however, its biological function and impact on pharmacokinetics in the intestine remain unclear. The present study, therefore, aimed to clarify the relationship between SAP-1 and the intestinal absorption behaviors of typical transporter substrates and macromolecules...
April 18, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28407399/abnormal-rab11-rab8-vesicles-cluster-in-enterocytes-of-patients-with-microvillus-inclusion-disease
#6
Georg F Vogel, Andreas R Janecke, Iris M Krainer, Karin Gutleben, Barbara Witting, Sally G Mitton, Sahar Mansour, Antje Ballauff, Joseph T Roland, Amy C Engevik, Ernest Cutz, Thomas Müller, James R Goldenring, Lukas A Huber, Michael W Hess
Microvillus inclusion disease (MVID) is a congenital enteropathy characterized by accumulation of vesiculo-tubular endomembranes in the subapical cytoplasm of enterocytes, historically termed "secretory granules." However, neither their identity nor pathophysiological significance is well defined. Using immunoelectron microscopy and tomography, we studied biopsies from MVID patients (3× Myosin 5b mutations and 1× Syntaxin3 mutation) and compared them to controls and genome-edited CaCo2 cell models, harboring relevant mutations...
April 13, 2017: Traffic
https://www.readbyqxmd.com/read/28369994/a-biomimetic-fly-photoreceptor-model-elucidates-how-stochastic-adaptive-quantal-sampling-provides-a-large-dynamic-range
#7
Zhuoyi Song, Mikko Juusola
Light intensities (photons s(-1)  μm(-2) ) in a natural scene vary over several orders of magnitude from shady woods to direct sunlight. A major challenge facing the visual system is how to map such a large dynamic input range into its limited output range, so that a signal is neither buried in noise in darkness nor saturated in brightness. A fly photoreceptor has achieved such a large dynamic range; it can encode intensity changes from single to billions of photons, outperforming man-made light sensors...
March 29, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28302370/the-lipid-5-phoshatase-ship2-controls-renal-brush-border-ultrastructure-and-function-by-regulating-the-activation-of-erm-proteins
#8
Sufyan G Sayyed, François Jouret, Marjorie Vermeersch, David Pérez-Morga, Stéphane Schurmans
The microvillus brush border on the renal proximal tubule epithelium allows the controlled reabsorption of solutes that are filtered through the glomerulus and thus participates in general body homeostasis. Here, using the lipid 5-phosphatase Ship2 global knockout mice, proximal tubule-specific Ship2 knockout mice, and a proximal tubule cell model in which SHIP2 is inactivated, we show that SHIP2 is a negative regulator of microvilli formation, thereby controlling solute reabsorption by the proximal tubule...
July 2017: Kidney International
https://www.readbyqxmd.com/read/28271233/regulation-of-glomerulotubular-balance-flow-activated-proximal-tubule-function
#9
REVIEW
Tong Wang, Sheldon Weinbaum, Alan M Weinstein
The purpose of this review is to summarize our knowledge and understanding of the physiological importance and the mechanisms underlying flow-activated proximal tubule transport. Since the earliest micropuncture studies of mammalian proximal tubule, it has been recognized that tubular flow is an important regulator of sodium, potassium, and acid-base transport in the kidney. Increased fluid flow stimulates Na(+) and HCO3(-) absorption in the proximal tubule via stimulation of Na/H-exchanger isoform 3 (NHE3) and H(+)-ATPase...
June 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28264818/trafficking-ion-transporters-to-the-apical-membrane-of-polarized-intestinal-enterocytes
#10
Amy Christine Engevik, James R Goldenring
Epithelial cells lining the gastrointestinal tract require distinct apical and basolateral domains to function properly. Trafficking and insertion of enzymes and transporters into the apical brush border of intestinal epithelial cells is essential for effective digestion and absorption of nutrients. Specific critical ion transporters are delivered to the apical brush border to facilitate fluid and electrolyte uptake. Maintenance of these apical transporters requires both targeted delivery and regulated membrane recycling...
March 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28174707/new-mouse-models-for-microvillus-inclusion-disease-mvid-where-do-the-inclusions-come-from-and-are-they-cause-or%C3%A2-consequence
#11
EDITORIAL
Lukas A Huber
No abstract text is available yet for this article.
March 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28123938/intestinal-invalidation-of-the-glucose-transporter-glut2-delays-tissue-distribution-of-glucose-and-reveals-an-unexpected-role-in-gut-homeostasis
#12
Charlotte C Schmitt, Thomas Aranias, Thomas Viel, Danielle Chateau, Maude Le Gall, Anne-Judith Waligora-Dupriet, Chloé Melchior, Ophélie Rouxel, Nathalie Kapel, Guillaume Gourcerol, Bertrand Tavitian, Agnès Lehuen, Edith Brot-Laroche, Armelle Leturque, Patricia Serradas, Alexandra Grosfeld
OBJECTIVE: Intestinal glucose absorption is orchestrated by specialized glucose transporters such as SGLT1 and GLUT2. However, the role of GLUT2 in the regulation of glucose absorption remains to be fully elucidated. METHODS: We wanted to evaluate the role of GLUT2 on glucose absorption and glucose homeostasis after intestinal-specific deletion of GLUT2 in mice (GLUT2(ΔIEC) mice). RESULTS: As anticipated, intestinal GLUT2 deletion provoked glucose malabsorption as visualized by the delay in the distribution of oral sugar in tissues...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28053225/the-v-atpase-is-expressed-in-the-choroid-plexus-and-mediates-camp-induced-intracellular-ph-alterations
#13
Henriette L Christensen, Teodor G Păunescu, Vladimir Matchkov, Dagne Barbuskaite, Dennis Brown, Helle H Damkier, Jeppe Praetorius
The cerebrospinal fluid (CSF) pH influences brain interstitial pH and, therefore, brain function. We hypothesized that the choroid plexus epithelium (CPE) expresses the vacuolar H(+)-ATPase (V-ATPase) as an acid extrusion mechanism in the luminal membrane to counteract detrimental elevations in CSF pH. The expression of mRNA corresponding to several V-ATPase subunits was demonstrated by RT-PCR analysis of CPE cells (CPECs) isolated by fluorescence-activated cell sorting. Immunofluorescence and electron microscopy localized the V-ATPase primarily in intracellular vesicles with only a minor fraction in the luminal microvillus area...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28034633/glycol-chitosan-a-stabilizer-of-lipid-rafts-in-the-intestinal-brush-border
#14
E Thomas Danielsen, E Michael Danielsen
Chitosan is a polycationic polysaccharide consisting of β-(1-4)-linked glucosamine units and due to its mucoadhesive properties, chemical derivatives of chitosan are potential candidates as enhancers for transmucosal drug delivery. Recently, glycol chitosan (GC), a soluble derivative of chitosan, was shown to bind specifically to lipid raft domains in model bilayers. The small intestinal brush border membrane has a unique lipid raft composition with high amounts of glycolipids cross-linked by lectins, and the aim of the present work therefore was to study the interaction of FITC-conjugated GC (FITC-GC) with the small intestinal epithelium...
December 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28027573/defects-in-myosin-vb-are-associated-with-a-spectrum-of-previously-undiagnosed-low-%C3%AE-glutamyltransferase-cholestasis
#15
Yi-Ling Qiu, Jing-Yu Gong, Jia-Yan Feng, Ren-Xue Wang, Jun Han, Teng Liu, Yi Lu, Li-Ting Li, Mei-Hong Zhang, Jonathan A Sheps, Neng-Li Wang, Yan-Yan Yan, Jia-Qi Li, Lian Chen, Christoph H Borchers, Bence Sipos, A S Knisely, Victor Ling, Qing-He Xing, Jian-She Wang
Hereditary cholestasis in childhood and infancy with normal serum gamma-glutamyltransferase (GGT) activity is linked to several genes. Many patients, however, remain genetically undiagnosed. Defects in myosin VB (MYO5B; encoded by MYO5B) cause microvillus inclusion disease (MVID; MIM251850) with recurrent watery diarrhea. Cholestasis, reported as an atypical presentation in MVID, has been considered a side effect of parenteral alimentation. Here, however, we report on 10 patients who experienced cholestasis associated with biallelic, or suspected biallelic, mutations in MYO5B and who had neither recurrent diarrhea nor received parenteral alimentation...
May 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27984607/-phenotypic-and-genetic-analysis-of-a-family-affected-with-microvillus-inclusion-disease
#16
Man Mao, Li Guo, Zhanhui Zhang, Bin Wang, Shanhua Huang, Yuanzong Song, Fengping Chen, Wangrong Wen
OBJECTIVE: To explore the clinical features and mutations of MYO5B gene in a family affected with microvillus inclusion disease. METHODS: Clinical data of an infant affected with microvillus inclusion disease was collected. Genomic DNA was extracted from peripheral blood samples from the patient and her parents. PCR amplification and Sanger sequencing were performed to analyze all the exons and their flanking sequences of the MYO5B gene. RESULTS: The patient presented with complicated manifestations including respiratory distress syndrome, dehydration, acidosis, bowel dilatation, liver and kidney dysfunction, and severe and intractable diarrhea...
December 10, 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/27933652/nonobstructive-diffuse-dilated-bowel-loops-prenatal-diagnosis-fetal-characteristics-and-neonatal-outcomes
#17
Guy Katz, Ben Pode-Shakked, Michal Berkenstadt, Ron Bilik, Sylvie Polak Charcon, Iris Barshack, Reuven Achiron, Yinon Gilboa
OBJECTIVES: The purpose of this study was to describe the characteristics and outcomes of fetuses with a diagnosis of nonobstructive diffuse dilated bowel loops. METHODS: We conducted a retrospective study of all pregnancies with fetal diagnosis of nonobstructive diffuse dilated bowel loops over 14 years in a large tertiary referral center. Fetomaternal and neonatal characteristics and outcomes were assessed. RESULTS: Seven fetuses had sonograms showing diffuse dilated bowel loops; none of them had intestinal obstruction after labor...
January 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/27856525/microvilli-morphology-can-affect-efflux-active-p-glycoprotein-in-confluent-mdckii-nki_hmdr1-and-caco-2-cell-monolayers
#18
Zhou Meng, Sylvain Le Marchand, Deep Agnani, Matt Szapacs, Harma Ellens, Joe Bentz
From fits of drug transport kinetics across confluent MDCKII-hMDR1-NKI and Caco-2 cell monolayers we estimated the levels of efflux active P-glycoprotein (P-gp) in these two cell lines (companion paper, Meng at el., 2016a). In the present work, we compared the efflux active P-gp number to the total P-gp level, using LC/MSMS, and showed that in Caco-2 cells total P-gp is about 10-fold greater than efflux active P-gp, while in MDCKII-hMDR1-NKI cells these values are within 2-fold. We further visualized the microvilli in MDCKII-hMDR1-NKI and Caco-2 cells using three-dimensional structured illumination super-resolution microscopy and found that the microvilli in Caco-2 cells are taller and more densely packed than those in MDCK-NKI-hMDR1 cells...
November 16, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27771587/study-on-the-effects-of-gradient-mechanical-pressures-on-the-proliferation-apoptosis-chondrogenesis-and-hypertrophy-of-mandibular-condylar-chondrocytes-in-vitro
#19
Hui Li, Linjian Huang, Qianyang Xie, Xieyi Cai, Chi Yang, Shaoyi Wang, Min Zhang
OBJECTIVE: To investigate the effects of gradient mechanical pressure on chondrocyte proliferation, apoptosis, and the expression of markers of chondrogenesis and chondrocyte hypertrophy. METHODS: Mandibular condylar chondrocytes from 5 rabbits were cultured in vitro, and pressed with static pressures of 50kPa, 100kPa, 150kPa and 200kPa for 3h, respectively. The chondrocytes cultured without pressure (0kPa) were used as control. Cell proliferation, apoptosis, and the expression of aggrecan (AGG), collagen II (COL2), collagen X (COL10), alkaline phosphatase (ALP) were investigated...
January 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/27646280/igg-trafficking-in-the-adult-pig-small-intestine-one-or-bidirectional-transfer-across-the-enterocyte-brush-border
#20
Rebecca Möller, Gert H Hansen, E Michael Danielsen
Immunoglobulin G (IgG) transfer in opposite directions across the small intestinal brush border serves different purposes in early life and in adulthood. In the neonate, maternal IgG is taken up from the gut lumen into the blood, conferring passive immunity to the offspring, whereas in the adult immunoglobulins, including IgG made by plasma cells in the lamina propria, are secreted via the brush border to the lumen as part of the mucosal defense. Here, IgG has been proposed to perform a luminal immune surveillance which eventually includes a reuptake through the brush border as pathogen-containing immune complexes...
March 2017: Histochemistry and Cell Biology
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