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Small membrane protein regulator

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https://www.readbyqxmd.com/read/29348617/neuronal-lysosomal-dysfunction-releases-exosomes-harboring-app-c-terminal-fragments-and-unique-lipid-signatures
#1
André M Miranda, Zofia M Lasiecka, Yimeng Xu, Jessi Neufeld, Sanjid Shahriar, Sabrina Simoes, Robin B Chan, Tiago Gil Oliveira, Scott A Small, Gilbert Di Paolo
Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29346527/progesterone-effects-on-extracellular-vesicles-in-the-sheep-uterus
#2
Gregory W Burns, Kelsey E Brooks, Eleanore V O'Neil, Darren E Hagen, Susanta K Behura, Thomas E Spencer
Progesterone (P4) acts via the endometrium to promote conceptus growth and implantation for pregnancy establishment. Many cells release extracellular vesicles (EVs) that are membrane-bound vesicles of endosomal and plasma membrane origin. In sheep, endometrial-derived EVs were found to traffic to the conceptus trophectoderm. Thus, EVs are hypothesized to be an important mode of intercellular communication by transferring select RNAs, proteins, and lipids between the endometrium and conceptus. Electron microscopy analysis found that the endometrial luminal and glandular epithelia were the primary source of EVs in the uterus of cyclic sheep...
January 16, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29344147/systematic-analysis-of-the-molecular-mechanism-of-microrna-124-in-hepatoblastoma-cells
#3
Guiming Wang, Hong Liu, Zhigang Wei, Hongyan Jia, Yu Liu, Jiansheng Liu
The present study aimed to identify the molecular mechanisms of microRNA-124 (miRNA-124/miR-124) in hepatoblastoma. The GSE6207 microarray dataset, obtained from the Gene Expression Omnibus database, included samples extracted from HepG2 cells transfected with miR-124 duplex (the experimental group) or negative control (the control group) at 4, 8, 16, 24, 32, 72 and 120 h after transfection. Differentially expressed genes (DEGs) were screened between the two groups. miR-124 activity was inferred based on the expression of its target genes...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343765/regulation-of-signaling-pathways-involved-in-the-anti-proliferative-and-apoptosis-inducing-effects-of-m22-against-non-small-cell-lung-adenocarcinoma-a549-cells
#4
Yao Yuan, Jiewei Wu, Bailin Li, Jia Niu, Haibo Tan, Shengxiang Qiu
The compound 29-(4-methylpiperazine)-luepol (M22), a novel derivative of lupeol has shown anti-proliferative effects against the human non-small cell lung cancer A549 cell line. M22 showed significant anti-proliferative activity at 6.80 μM and increased accumulation of G1 cells and effectively suppressed expression of the G1 arrest-related genes cyclins D1 and E1, CDK2 and CDC25A. This was further confirmed by Western blotting demonstrating decreased cyclin D1 and CDC25A protein levels. Furthermore, M22 caused induction of apoptosis that downregulated the anti-apoptotic BCL-2 gene and increased expression of BAX, CASP3 and CASP9 as well as the APAF1 gene...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342938/role-of-aquaporins-in-determining-carbon-and-nitrogen-status-in-higher-plants
#5
REVIEW
Limin Gao, Zhifeng Lu, Lei Ding, Junjie Guo, Min Wang, Ning Ling, Shiwei Guo, Qirong Shen
Aquaporins (AQPs) are integral membrane proteins facilitating the transport of water and some small neutral molecules across cell membranes. In past years, much effort has been made to reveal the location of AQPs as well as their function in water transport, photosynthetic processes, and stress responses in higher plants. In the present review, we paid attention to the character of AQPs in determining carbon and nitrogen status. The role of AQPs during photosynthesis is characterized as its function in transporting water and CO₂ across the membrane of chloroplast and thylakoid; recalculated results from published studies showed that over-expression of AQPs contributed to 25% and 50% increases in stomatal conductance (gs) and mesophyll conductance (gm), respectively...
January 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29339453/pgrmc1-localization-and-putative-function-in-the-nucleolus-of-bovine-granulosa-cells-and-oocytes
#6
Laura Terzaghi, Alberto Maria Luciano, Priscila C Dall Acqua, Silvia Modina, John J Peluso, Valentina Lodde
Progesterone Receptor Membrane Component-1 (PGRMC1) is a highly conserved multifunctional protein that is found in numerous systems, including reproductive system. Interestingly, PGRMC1 is expressed at several intracellular locations, including the nucleolus. The aim of this study is to investigate the functional relationship between PGRMC1 and nucleolus. Immunofluorescence experiments confirmed PGRMC1's nucleolar localization in cultured bovine granulosa cells (bGC) and oocytes. Additional experiments conducted on bGC revealed that PGRMC1 co-localizes with nucleolin (NCL), a major nucleolar protein...
January 16, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29338771/regulation-of-aquaporins-in-plants-under-stress
#7
REVIEW
Ranganathan Kapilan, Maryam Vaziri, Janusz J Zwiazek
Aquaporins (AQP) are channel proteins belonging to the Major Intrinsic Protein (MIP) superfamily that play an important role in plant water relations. The main role of aquaporins in plants is transport of water and other small neutral molecules across cellular biological membranes. AQPs have remarkable features to provide an efficient and often, specific water flow and enable them to transport water into and out of the cells along the water potential gradient. Plant AQPs are classified into five main subfamilies including the plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), nodulin 26 like intrinsic proteins (NIPs), small basic intrinsic proteins (SIPs) and X intrinsic proteins (XIPs)...
January 16, 2018: Biological Research
https://www.readbyqxmd.com/read/29337043/membrane-permeable-rab27a-is-a-regulator-of-the-acrosome-reaction-role-of-geranylgeranylation-and-guanine-nucleotides
#8
Matías A Bustos, Ornella Lucchesi, María C Ruete, Claudia N Tomes
The acrosome reaction is the regulated exocytosis of mammalian sperm's single secretory granule, essential for fertilization. It relies on small GTPases, the cAMP binding protein Epac, and the SNARE complex, among other components. Here, we describe a novel tool to investigate Rab27-related signaling pathways: a hybrid recombinant protein consisting of human Rab27A fused to TAT, a cell penetrating peptide. With this tool, we aimed to unravel the connection between Rab3, Rab27 and Rap1 in sperm exocytosis and to deepen our understanding about how isoprenylation and guanine nucleotides influence the behaviour of Rab27 in exocytosis...
January 11, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29331415/nogo-b-receptor-promotes-epithelial-mesenchymal-transition-in-non-small-cell-lung-cancer-cells-through-the-ras-erk-snail1-pathway
#9
Donghua Wu, Baofeng Zhao, Xiaoyu Qi, Fang Peng, Hailu Fu, Xinming Chi, Qing Robert Miao, Shujuan Shao
Nogo-B receptor (NgBR) is a specific receptor of Nogo-B that regulates vascular remodeling and angiogenesis. Previously, we found that NgBR promotes the membrane translocation and activation of Ras in breast cancer cells and enhances the chemoresistance of hepatocellular carcinoma cells to 5-fluorouracil. However, the role of NgBR in lung cancer has not yet been elucidated. In the present study, we found that NgBR knockdown inhibited epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells in vitro and metastasis of NSCLC cells in vivo...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330887/loss-of-vamp5-in-mice-results-in-duplication-of-the-ureter-and-insufficient-expansion-of-the-lung
#10
Maiko Ikezawa, Yuki Tajika, Hitoshi Ueno, Tohru Murakami, Naokazu Inoue, Hiroshi Yorifuji
BACKGROUND: VAMP5 is a member of the SNARE protein family, which regulate the docking and fusion of membrane vesicles within cells. Previously, we reported ubiquitous expression of VAMP5 proteins in various organs except the brain and small intestine. However, the precise roles of VAMP5 in each organ remain unclear. To explore the roles of VAMP5 in vivo, we generated VAMP5 knockout (KO) mice. RESULTS: VAMP5 KO mice showed low birth rate and low body weight. KO embryos grew normally in the uterus, and tended to die around birth...
January 13, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29321663/lpa-signaling-is-regulated-through-the-primary-cilium-a-novel-target-in-glioblastoma
#11
Yuriy V Loskutov, Caryn L Griffin, Kristina M Marinak, Andrey Bobko, Naira V Margaryan, Werner J Geldenhuys, Jann N Sarkaria, Elena N Pugacheva
The primary cilium is a ubiquitous organelle presented on most human cells. It is a crucial signaling hub for multiple pathways including growth factor and G-protein coupled receptors. Loss of primary cilia, observed in various cancers, has been shown to affect cell proliferation. Primary cilia formation is drastically decreased in glioblastoma (GBM), however, the role of cilia in normal astrocyte or glioblastoma proliferation has not been explored. Here, we report that loss of primary cilia in human astrocytes stimulates growth rate in a lysophosphatidic acid (LPA)-dependent manner...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29318594/partial-rescue-of-f508del-cftr-channel-gating-with-modest-improvement-of-protein-processing-but-not-stability-by-a-dual-acting-small-molecule
#12
Jia Liu, Hermann Bihler, Carlos M Farinha, Nikhil T Awatade, Ana M Romão, Dayna Mercadante, Yi Cheng, Isaac Musisi, Walailak Jantarajit, Yiting Wang, Zhiwei Cai, Margarida D Amaral, Martin Mense, David N Sheppard
BACKGROUND AND PURPOSE: Rescue of F508del-cystic fibrosis transmembrane conductance regulator (CFTR), the most common cystic fibrosis (CF) mutation, requires small molecules that overcome protein processing, stability and channel gating defects. Here, we investigate F508del-CFTR rescue by CFFT-004 (from WO2010/068863), a small molecule designed to independently correct protein processing and channel gating defects. EXPERIMENTAL APPROACH: Using CFTR-expressing recombinant cells and CF patient-derived bronchial epithelial cells, we studied CFTR expression by Western blotting and channel gating and stability with the patch-clamp and Ussing chamber techniques...
January 10, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29313986/protein-kinase-d-activation-induces-mitochondrial-fragmentation-and-dysfunction-in-cardiomyocytes
#13
Bong Sook Jhun, Jin O-Uchi, Stephanie M Adaniya, Tomas J Mancini, Jessica L Cao, Michelle E King, Amy K Landi, Hanley Ma, Milla Shin, Donqin Yang, Xiaole Xu, Yisang Yoon, Gaurav Choudhary, Richard T Clements, Ulrike Mende, Shey-Shing Sheu
Regulation of mitochondrial morphology is crucial for the maintenance of physiological functions in many cell types including cardiomyocytes. Small and fragmented mitochondria are frequently observed in pathological condition, but it is still unclear which cardiac signalling pathway is responsible for regulating the abnormal mitochondrial morphology in cardiomyocytes. Here we demonstrate that a downstream kinase of Gq -protein coupled receptor (Gq PCR) signalling, protein kinase D (PKD), mediates pathophysiological modifications in mitochondrial morphology and function, which consequently contribute to the activation of apoptotic signalling...
January 5, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29311138/bacterial-outer-membrane-vesicles-from-dextran-sulfate-sodium-induced-colitis-differentially-regulate-intestinal-udp-glucuronosyltransferase-1a1-partially-through-tlr4-mapk-pi3k-pathway
#14
Xuejiao Gao, Ting Li, Bin Wei, Zhixiang Yan, Nan Hu, Yanjuan Huang, Beilei Han, Tai-Seng Wai, Wei Yang, Ru Yan
UDP-glucuronosyltransferase 1A1 (UGT1A1) constitutes an important part of intestinal epithelial barrier and catalyzes glucuronidation of many endogenous compounds and drugs. Down-regulation of UGT1A1 in inflammation has been reported, while the association with gut dysbiosis is poorly defined. This study verified the involvement of gut microbiota in intestinal UGT1A1 regulation using dextran sulfate sodium (DSS)-induced rat colitis model plus fecal microbiota transplantation (FMT). Generally, both DSS induction and colitis-to-normal FMT suppressed mRNA and protein expressions of UGT1A1 and nuclear xenobiotic receptors (NRs) in colon, but enhanced mRNA and decreased protein of rUGT1A1/rNRs in small intestine...
January 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29304561/crosstalk-between-cellular-redox-state-and-the-anti-apoptotic-protein-bcl-2
#15
Sebastian Other-Gee Pohl, Mark Agostino, Arun Dharmarajan, Shazib Pervaiz
SIGNIFICANCE B cell lymphoma-2 (Bcl-2) is the prototypical anti-apoptotic member of the Bcl-2 family that comprises proteins with contrasting effects on cell fate. Identified as a consequence chromosomal translocation (t 14:18) in human lymphoma, subsequent studies have revealed mutations and/or copy number alterations, as well as post-translational modifications, of Bcl-2 in a variety of cancers. The canonical function of Bcl-2 is linked to its ability to inhibit mitochondrial membrane permeabilization, regulating apoptosome assembly and activation by blocking cytosolic translocation of death amplification factors...
January 5, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29303613/cellular-differentiation-of-non-transformed-intestinal-epithelial-cells-is-regulated-by-lactobacillus-rhamnosus-and-l-casei-strains
#16
J Kolinska, M Zakostelecka, Z Zemanova, V Lisa, J Golias, H Kozakova, B Dvorak
The aim of this study was to characterize an in vitro modulating effect of three commensal Lactobacillus strains on cellular differentiation of non-transformed crypt-like rat small intestinal cell line IEC-18. IEC-18 was grown on extracellular matrix (ECM), with or without presence of Lactobacillus strains. Gene expression of IEC-18 bacterial detection system - such as Toll-like receptors TLR-2, TLR-4, signal adapter MyD88, cytoplasmic NOD2 receptor, inflammatory cytokines IL-18, IL-1beta, chemokine IL-8 and enzyme caspase-1 - was evaluated using real-time PCR...
January 5, 2018: Physiological Research
https://www.readbyqxmd.com/read/29286340/slc9a3-protein-is-critical-for-acrosomal-formation-in-postmeiotic-male-germ-cells
#17
Ya-Yun Wang, Han-Sun Chiang, Chiao-Yin Cheng, Yi-No Wu, Yung-Chih Lin, Hsuan-Che Liu, Wei-Kung Tsai, Yen-Lin Chen, Ying-Hung Lin
Solute carrier family 9 isoform 3 (SLC9A3), a Na⁺/H⁺ exchanger, regulates the transepithelial absorption of Na⁺ and water and is primarily expressed on the apical membranes of the intestinal epithelium, renal proximal tubule, epididymis, and vas deferens. Loss of the Slc9a3 allele in mice enhances intestinal fluid and causes diarrhoea as a consequence of diminished Na⁺ and HCO₃- absorption. Hence, the loss also causes male infertility and reveals the abnormal dilated lumen of the rete testis and calcification in efferent ductules...
December 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29283339/kai1-cd82-metastasis-suppressor-gene-as-a-therapeutic-target-for-non-small-cell-lung-carcinoma
#18
Venugopal Vinod Prabhu, S Niranjali Devaraj
Lung cancer is the most frequent malignancy and the leading cause of cancer-related death worldwide; it is the second most common cancer, comprising 1.69 million deaths worldwide per year. Among these, 85% of lung cancers are non-small-cell lung carcinoma (NSCLC). Metastasis is common in NSCLC patients and are responsible for most deaths. Kang-Ai 1 (KAI1), a tumor metastasis suppressor gene also known as Cluster of Differentiation 82 (CD82), is a member of the membrane tetraspanin protein family, which are capable of inhibiting the metastatic process in NSCLC...
2017: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29281629/loss-of-function-of-the-ciliopathy-protein-cc2d2a-disorganizes-the-vesicle-fusion-machinery-at-the-periciliary-membrane-and-indirectly-affects-rab8-trafficking-in-zebrafish-photoreceptors
#19
Irene Ojeda Naharros, Matthias Gesemann, José M Mateos, Gery Barmettler, Austin Forbes, Urs Ziegler, Stephan C F Neuhauss, Ruxandra Bachmann-Gagescu
Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors...
December 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29244804/conditional-knockout-mice-for-the-distal-appendage-protein-cep164-reveal-its-essential-roles-in-airway-multiciliated-cell-differentiation
#20
Saul S Siller, Himanshu Sharma, Shuai Li, June Yang, Yong Zhang, Michael J Holtzman, Wipawee Winuthayanon, Holly Colognato, Bernadette C Holdener, Feng-Qian Li, Ken-Ichi Takemaru
Multiciliated cells of the airways, brain ventricles, and female reproductive tract provide the motive force for mucociliary clearance, cerebrospinal fluid circulation, and ovum transport. Despite their clear importance to human biology and health, the molecular mechanisms underlying multiciliated cell differentiation are poorly understood. Prior studies implicate the distal appendage/transition fiber protein CEP164 as a central regulator of primary ciliogenesis; however, its role in multiciliogenesis remains unknown...
December 15, 2017: PLoS Genetics
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