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Small membrane protein regulator

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https://www.readbyqxmd.com/read/27915045/in-vivo-selection-of-heterotypically-interacting-transmembrane-helices-complementary-helix-surfaces-rather-than-conserved-interaction-motifs-drive-formation-of-transmembrane-hetero-dimers
#1
Dominik Steindorf, Dirk Schneider
Single pass transmembrane proteins make up almost half of the whole transmembrane proteome. Contacts between such bitopic transmembrane proteins are common, and oligomerization of their single transmembrane helix is involved in triggering and regulation of signal transduction across cell membranes. In several recent analyses the distribution of amino acids at helix-helix contact sides has been analyzed, and e.g. a preference of amino acids with small side chains has been identified. Here we select amino acids, amino acid pairings and amino acid motifs, which mediate strong interactions of single-span transmembrane α-helices...
November 30, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27911840/multistep-regulation-of-autophagy-by-wnk1
#2
Sachith Gallolu Kankanamalage, A-Young Lee, Chonlarat Wichaidit, Andres Lorente-Rodriguez, Akansha M Shah, Steve Stippec, Angelique W Whitehurst, Melanie H Cobb
The with-no-lysine (K) (WNK) kinases are an atypical family of protein kinases that regulate ion transport across cell membranes. Mutations that result in their overexpression cause hypertension-related disorders in humans. Of the four mammalian WNKs, only WNK1 is expressed throughout the body. We report that WNK1 inhibits autophagy, an intracellular degradation pathway implicated in several human diseases. Using small-interfering RNA-mediated WNK1 knockdown, we show autophagosome formation and autophagic flux are accelerated...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27897225/calmodulin-interacts-with-rab3d-and-modulates-osteoclastic-bone-resorption
#3
Sipin Zhu, Shek Man Chim, Taksum Cheng, Estabelle Ang, Benjamin Ng, Baysie Lim, Kai Chen, Heng Qiu, Jennifer Tickner, Huazi Xu, Nathan Pavlos, Jiake Xu
Calmodulin is a highly versatile protein that regulates intracellular calcium homeostasis and is involved in a variety of cellular functions including cardiac excitability, synaptic plasticity and signaling transduction. During osteoclastic bone resorption, calmodulin has been reported to concentrate at the ruffled border membrane of osteoclasts where it is thought to modulate bone resorption activity in response to calcium. Here we report an interaction between calmodulin and Rab3D, a small exocytic GTPase and established regulator osteoclastic bone resorption...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27893811/the-inhibition-of-microrna-128-on-igf-1-activating-mtor-signaling-involves-in-temozolomide-induced-glioma-cell-apoptotic-death
#4
Peng-Hsu Chen, Chia-Hsiung Cheng, Chwen-Ming Shih, Kuo-Hao Ho, Cheng-Wei Lin, Chin-Cheng Lee, Ann-Jeng Liu, Cheng-Kuei Chang, Ku-Chung Chen
Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death...
2016: PloS One
https://www.readbyqxmd.com/read/27890709/role-of-major-and-brain-specific-sgce-isoforms-in-the-pathogenesis-of-myoclonus-dystonia-syndrome
#5
Jianfeng Xiao, Satya R Vemula, Yi Xue, Mohammad M Khan, Francesca A Carlisle, Adrian J Waite, Derek J Blake, Ioannis Dragatsis, Yu Zhao, Mark S LeDoux
Loss-of-function mutations in SGCE, which encodes ε-sarcoglycan (ε-SG), cause myoclonus-dystonia syndrome (OMIM159900, DYT11). A "major" ε-SG protein derived from CCDS5637.1 (NM_003919.2) and a "brain-specific" protein, that includes sequence derived from alternative exon 11b (CCDS47642.1, NM_001099400.1), are reportedly localized in post- and pre-synaptic membrane fractions, respectively. Moreover, deficiency of the "brain-specific" isoform and other isoforms derived from exon 11b may be central to the pathogenesis of DYT11...
November 24, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27885275/tdb-protects-vascular-endothelial-cells-against-oxygen-glucose-deprivation-reperfusion-induced-injury-by-targeting-mir-34a-to-increase-bcl-2-expression
#6
Li-Xi Liao, Ming-Bo Zhao, Xin Dong, Yong Jiang, Ke-Wu Zeng, Peng-Fei Tu
Prolonged ischemia can result in apoptotic death of vascular endothelial cells and lead to ischemic vascular diseases including vascular dementia, arteriosclerosis and brain oedema. Finding protective strategies to prevent this is therefore an urgent mission. Recent studies have shown that dysregulation of microRNAs (miRNAs) can lead to imbalance of Bcl-2 family proteins and mitochondrial dysfunction, leading to further damage of vascular cells under ischemic conditions. However, whether miRNAs can be used as a drug target for treating vascular diseases is not fully understood...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881679/the-shigella-virulence-factor-icsa-relieves-n-wasp-autoinhibition-by-displacing-the-vca-domain
#7
Rui P M Mauricio, Cy M Jeffries, Dmitri I Svergun, Janet E Deane
Shigella flexneri is a bacterial pathogen that invades cells of the gastrointestinal tract causing severe dysentery. Shigella mediate intracellular motility and spreading via actin comet tail formation. This process is dependent on the surface-exposed, membrane-embedded virulence factor IcsA, which recruits the host actin regulator N-WASP. Although it is clear that Shigella require N-WASP for this process, the molecular details of this interaction and the mechanism of N-WASP activation remain poorly understood...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27865700/adhesion-ability-of-angiotensin-ii-with-model-membranes
#8
Julia Preu, Louis Tiefenauer, Thomas Gutberlet
The octa-peptide angiotensin II (Ang II, (H2NAspArgValTyrIleHisProPheCOOH)) is one of the key player on blood pressure regulation in mammals. Predominantly binding to the Angiotensin type 1 and 2 receptors, the hormone is one of several peptide ligands binding to G protein coupled receptors (GPCR). The active hormone derives from a high molecular weight precursor sequentially cleaved by the proteases renin and the angiotensin converting enzyme (ACE). The chemical nature of the amino acid sequence has an impact on the behavior in the proximity of membranes, demonstrated using different membrane model systems and biophysical methods...
November 17, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27859863/the-influence-of-very-small-doses-of-alpha-radiation-on-the-stability-of-erythrocytes
#9
Magdalena Kaczmarska, Dominika Żydek, Justyna Wilkłacz-Potoczny, Maria Fornal, Tomasz Grodzicki, Elżbieta Kochowska, Krzysztof Kozak, Łukasz Gocal, Władysław Pohorecki, Krzysztof Matlak, Józef Korecki, Květoslava Burda
Our aim was to study the influence of low doses (0.2-4 μGy) of α radiation on the stability of human erythrocytes isolated from healthy and diabetic erythrocytes. Absorption spectroscopy was used to measure the level of red blood cell (RBC) hemolysis, along with Mössbauer spectroscopy, which is a highly specific method suited to monitoring various hemoglobin forms. States of hemoglobin are sensitive to a homeostatic imbalance in red blood cells. Changes in the membrane skeleton organization of irradiated erythrocytes isolated from healthy donors were studied using atomic force microscopy (AFM)...
November 16, 2016: Microscopy Research and Technique
https://www.readbyqxmd.com/read/27857971/cyclin-d1-promotes-tumor-cell-invasion-and-metastasis-by-cytoplasmic-mechanisms
#10
Noel P Fusté, Francisco Ferrezuelo, Eloi Garí
Amplification of cyclin D1 is a frequent alteration in many cancers of different type and origin. We recently described a novel regulatory axis involving cyclin D1 in the regulation of tumor invasion and metastasis. Membrane-associated cyclin D1-CDK4 complexes promote activation of the small GTPase RAC1 through phosphorylation of the regulatory protein paxillin.
2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27852864/palmitoylation-of-sindbis-virus-tf-protein-regulates-its-plasma-membrane-localization-and-subsequent-incorporation-into-virions
#11
Jolene Ramsey, Emily C Renzi, Randy J Arnold, Jonathan C Trinidad, Suchetana Mukhopadhyay
: Palmitoylation is a reversible, post-translational modification that helps target proteins to cellular membranes. The alphavirus small membrane proteins 6K and TF have been reported to be palmitoylated and to positively regulate budding. 6K and TF are isoforms identical in the N-terminus but unique in the C-terminus due to a (-1) ribosomal frameshift during translation. In this study we used cysteine (Cys) mutants to test differential palmitoylation of Sindbis virus 6K and TF proteins...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27852857/hepatitis-c-virus-induced-rab32-aggregation-and-its-implication-in-virion-assembly
#12
Tu M Pham, Si C Tran, Yun-Sook Lim, Soon B Hwang
: Hepatitis C virus (HCV) is highly dependent on cellular factors for viral propagation. Using high-throughput next-generation sequencing, we analyzed the host transcriptomic changes and identified 30 candidate genes which were up-regulated in cell culture-grown HCV (HCVcc)-infected cells. Of these candidates, we selected Rab32 for further investigation. Rab32 is a small GTPase that regulates a variety of intracellular membrane-trafficking events in various cell types. In this study, we demonstrated that both mRNA and protein levels of Rab32 were increased in HCV-infected cells...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27846718/-rab-proteins-intracellular-transport-and-cancer
#13
R Černochová, M Nekulová, J Holčaková
BACKGROUND: Rab proteins are small monomeric enzymes which belong to the large Ras protein superfamily and allow hydrolysis of guanosine triphosphate (GTP) to guanosine (GDP). Up to now more than 60 proteins have been described that act primarily as regulators of intracellular transport. Rab GTPases are mostly located at the intracellular membranes, where they provide connections to motor proteins and to the cytoskeleton and control various steps of the traffic pathways including the formation and movement of vesicles or membrane fusion controlling secretion, endocytosis, recycling and degradation of proteins...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27837347/tamoxifen-resistance-and-metastasis-of-human-breast-cancer-cells-were-mediated-by-the-membrane-associated-estrogen-receptor-er-%C3%AE-36-signaling-in-vitro
#14
Wenwen Gu, Nian Dong, Peng Wang, Changgen Shi, Jun Yang, Jian Wang
The drug resistance and tumor metastasis have been the main obstacles for the longer-term therapeutic effects of tamoxifen (TAM) on estrogen receptor-positive (ER(+)) breast cancer, but the mechanisms underlying the TAM resistance are still unclear. Here, we demonstrated that the membrane-associated estrogen receptor ER-α36 signaling, but not the G protein-coupled estrogen receptor 1 (GPER1) signaling, might be involved in the TAM resistance and metastasis of breast cancer cells. In this study, a model of ER(+) breast cancer cell MCF-7 that involves the up-regulated expression of ER-α36 and unchanged expression of ER-α66 and GPER1 was established via the removal of insulin from the cell culture medium...
November 11, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27833910/extracellular-microvesicle-production-by-human-eosinophils-activated-by-inflammatory-stimuli
#15
Praveen Akuthota, Lívia A S Carmo, Kennedy Bonjour, Ryann O Murphy, Thiago P Silva, Juliana P Gamalier, Kelsey L Capron, John Tigges, Vasilis Toxavidis, Virginia Camacho, Ionita Ghiran, Shigeharu Ueki, Peter F Weller, Rossana C N Melo
A key function of human eosinophils is to secrete cytokines, chemokines and cationic proteins, trafficking, and releasing these mediators for roles in inflammation and other immune responses. Eosinophil activation leads to secretion of pre-synthesized granule-stored mediators through different mechanisms, but the ability of eosinophils to secrete extracellular vesicles (EVs), very small vesicles with preserved membrane topology, is still poorly understood. In the present work, we sought to identify and characterize EVs released from human eosinophils during different conditions: after a culturing period or after isolation and stimulation with inflammatory stimuli, which are known to induce eosinophil activation and secretion: CCL11 (eotaxin-1) and tumor necrosis factor alpha (TNF-α)...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27827364/structural-and-mechanistic-insights-into-regulation-of-the-retromer-coat-by-tbc1d5
#16
Da Jia, Jin-San Zhang, Fang Li, Jing Wang, Zhihui Deng, Mark A White, Douglas G Osborne, Christine Phillips-Krawczak, Timothy S Gomez, Haiying Li, Amika Singla, Ezra Burstein, Daniel D Billadeau, Michael K Rosen
Retromer is a membrane coat complex that is recruited to endosomes by the small GTPase Rab7 and sorting nexin 3. The timing of this interaction and consequent endosomal dynamics are thought to be regulated by the guanine nucleotide cycle of Rab7. Here we demonstrate that TBC1d5, a GTPase-activating protein (GAP) for Rab7, is a high-affinity ligand of the retromer cargo selective complex VPS26/VPS29/VPS35. The crystal structure of the TBC1d5 GAP domain bound to VPS29 and complementary biochemical and cellular data show that a loop from TBC1d5 binds to a conserved hydrophobic pocket on VPS29 opposite the VPS29-VPS35 interface...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27818889/discovery-of-the-molecular-mechanisms-of-the-novel-chalcone-based-magnaporthe-oryzae-inhibitor-c1-using-transcriptomic-profiling-and-co-expression-network-analysis
#17
Hui Chen, Xiaoyun Wang, Hong Jin, Rui Liu, Taiping Hou
BACKGROUND: In our previous studies, we discovered a series of chalcone-based phytopathogenic fungus inhibitors. However, knowledge of their effects, detailed targets and molecular mechanisms in Magnaporthe oryzae (M. oryzae) remained limited. METHODS: To explore the expression and function of differentially expressed genes in M. oryzae after treatment with compound C1, we analyzed the expression profile of mRNAs using a microarray analysis and GO, KEGG and WGCNA analysis, followed by qRT-PCR and Western blots to validate our findings...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27817195/mechanisms-underlying-lung-resistance-related-protein-lrp-mediated-doxorubicin-resistance-of-non-small-cell-lung-cancer-cells
#18
Yu-Lun Chen, Tsung-Ying Yang, Chieh-Liang Wu, Kun-Chieh Chen, Shih-Lan Hsu, Chi-Mei Hsueh
Lung resistance-related protein (LRP) is a human major vault protein (MVP) implicated in drug resistance of cancer cells in a cell-type dependent manner. The primary goal of the study was to understand the role(s) of LRP in doxorubicin (DOX) resistance of non-small cell lung cancer (NSCLC) cells and the underlying working mechanisms. In the study, the roles of LRP in the regulation of DOX dynamics, nuclear import of minor vault proteins (vPARP and TEP1) and DOX-mediated cytotoxicity were examined in CH27 and H460 cells...
December 31, 2016: Chinese Journal of Physiology
https://www.readbyqxmd.com/read/27809762/transcriptome-analysis-of-the-fungal-pathogen-fusarium-oxysporum-f-sp-medicaginis-during-colonisation-of-resistant-and-susceptible-medicago-truncatula-hosts-identifies-differential-pathogenicity-profiles-and-novel-candidate-effectors
#19
Louise F Thatcher, Angela H Williams, Gagan Garg, Sally-Anne G Buck, Karam B Singh
BACKGROUND: Pathogenic members of the Fusarium oxysporum species complex are responsible for vascular wilt disease on many important crops including legumes, where they can be one of the most destructive disease causing necrotrophic fungi. We previously developed a model legume-infecting pathosystem based on the reference legume Medicago truncatula and a pathogenic F. oxysporum forma specialis (f. sp.) medicaginis (Fom). To dissect the molecular pathogenicity arsenal used by this root-infecting pathogen, we sequenced its transcriptome during infection of a susceptible and resistant host accession...
November 3, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27808256/the-role-of-pericytic-laminin-in-blood-brain-barrier-integrity-maintenance
#20
Jyoti Gautam, Xuanming Zhang, Yao Yao
Laminin, a major component of the basement membrane, plays an important role in blood brain barrier regulation. At the neurovascular unit, brain endothelial cells, astrocytes, and pericytes synthesize and deposit different laminin isoforms into the basement membrane. It has been shown that laminin α4 (endothelial laminin) regulates vascular integrity at embryonic/neonatal stage, while astrocytic laminin maintains vascular integrity in adulthood. Here, we investigate the function of pericyte-derived laminin in vascular integrity...
November 3, 2016: Scientific Reports
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