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https://www.readbyqxmd.com/read/28743009/retromer
#1
María Lucas, Aitor Hierro
Lucas and Hierro introduce the retromer and its role in endosomal protein sorting and trafficking.
July 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28742344/insights-into-the-molybdenum-copper-heterometallic-cluster-assembly-in-the-orange-protein-probing-intermolecular-interactions-with-an-artificial-metal-binding-atcun-tag
#2
Biplab K Maiti, Rui M Almeida, Luisa B Maia, Isabel Moura, José J G Moura
Orange protein (ORP) is a small bacterial protein, of unknown function, that contains a unique molybdenum/copper heterometallic cluster, [S2Mo(VI)S2Cu(I)S2Mo(VI)S2](3-) (Mo/Cu), non-covalently bound. The native cluster can be reconstituted in a protein-assisted mode by the addition of Cu(II) plus tetrathiomolybdate to apo-ORP under controlled conditions. In the work described herein, we artificially inserted the ATCUN ("amino terminus Cu and Ni") motif in the Desulfovibrio gigas ORP (Ala1Ser2His3 followed by the native amino acid residues; modified protein abbreviated as ORP*) to increase our understanding of the Mo/Cu cluster assembly in ORP...
July 25, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28741726/ns1643-enhances-ionic-currents-in-a-g604s-wt-herg-co-expression-system-associated-with-long-qt-syndrome-2
#3
JianHua Huo, Xueyan Guo, Qun Lu, Hua Qiang, Ping Liu, Ling Bai, Christopher L H Huang, Yanmin Zhang, Aiqun Ma
Loss of function mutations in the human ether-a-go-go-related gene (hERG) cause long QT syndrome type 2 (LQT2). Most LQT2 patients are heterozygous mutation carriers in which the mutant hERG exerts potent dominant-negative effects. 1, 3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) is known to enhance IKr in WT-hERG. We investigated its actions following lipofectamine-induced expression of both mutant G604S- and WT-hERG in the heterologous HEK293 expression system. Cells transfected with pcDNA3-G604S-hERG did not lead to any expression of detectable currents whether before or following NS1643 challenge...
July 25, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28741486/rethinking-lymphatic-vessels-and-antitumor-immunity
#4
REVIEW
Amanda W Lund
Lymphatic vessels facilitate fluid homeostasis, immune cell trafficking, and lipid transport, and contribute to solid tumor progression as routes of metastasis. Given new evidence that lymphatic vessels both correlate with intratumoral lymphocytes and directly suppress immune function, I reevaluate the passive lymphatic vessel paradigm and discuss its relevance to antitumor immunity.
October 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741480/cadherins-glycans-in-cancer-sweet-players-in-a-bitter-process
#5
REVIEW
Sandra Carvalho, Celso A Reis, Salomé S Pinho
Cadherins are key components in tissue morphogenesis and architecture, contributing to the establishment of cohesive cell adhesion. Reduced cellular adhesiveness as a result of cadherin dysfunction is a defining feature of cancer. During tumor development and progression, major changes in the glycan repertoire of cancer cells take place, affecting the stability, trafficking, and cell-adhesion properties of cadherins. Importantly, the different glycoforms of cadherins are promising biomarkers, with potential clinical application to improve the management of patients, and constitute targets for the development of new therapies...
September 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741098/regulation-of-paclitaxel-activity-by-microtubule-associated-proteins-in-cancer-chemotherapy
#6
REVIEW
Xingjuan Shi, Xiaoou Sun
Microtubules, highly dynamic components of the cytoskeleton, participate in diverse cellular activities such as mitosis, cell migration, and intracellular trafficking. Dysregulation of microtubule dynamics contributes to the development of serious diseases, including cancer. The dynamic properties and functions of microtubule network are regulated by microtubule-associated proteins. Paclitaxel, an anti-microtubule agent of the taxane family, has shown a success in clinical treatment of many cancer patients...
July 24, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28740576/the-chemokine-scavenging-receptor-d6-ackr2-is-a-target-of-mir-146a-in-thyroid-cancer
#7
Francesco Pacifico, Alessio Lepore, Stefano Mellone, Luca Sanguigno, Giorgia Federico, Adelaide Greco, Arturo Brunetti, Antonio Leonardi
We have previously shown that miR-146a, a NF-κB-regulated microRNA, is strongly expressed in human specimens and cell lines derived from anaplastic thyroid carcinomas (ATC) where it mediates some of the NF-κB pro-tumorigenic functions. By using a bioinformatic analysis, we identified the chemokine scavenger receptor D6/ ACKR2 as a target of miR146a in human ATC. We found that the expression of D6/ ACKR2 was up-regulated in miR-146a-null ATC cell lines and that the 3' UTR of D6/ ACKR2 mRNA was able to inhibit its expression in parental, but not in miR-146a-null ATC cells...
May 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28739602/loss-of-prion-protein-is-associated-with-the-development-of-insulin-resistance-and-obesity
#8
Giovanna Brito, Fernada C S Lupinacci, Flávio H Beraldo, Tiago G Santos, Martin Roffé, Marilene H Lopes, Vladmir C C de Lima, Vilma R Martins, Glaucia N M Hajj
Prion protein (PrP(C)) was initially described due to its involvement in transmissible spongiform encephalopathies. It was subsequently demonstrated to be a cell surface molecule involved in many physiological processes, such as vesicle trafficking. Herein, we investigated the roles of PrP(C) in the response to insulin and obesity development.  Two independent PrP(C) knockout (KO) and one PrP(C) overexpressing (TG20) mouse models were fed high-fat diets, and the development of insulin resistance and obesity was monitored...
July 24, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28739288/recent-advances-on-extracellular-vesicles-in-therapeutic-delivery-challenges-solutions-and-opportunities
#9
REVIEW
Mei Lu, Haonan Xing, Zhen Yang, Yanping Sun, Tianzhi Yang, Xiaoyun Zhao, Cuifang Cai, Dongkai Wang, Pingtian Ding
Extracellular vesicles (EVs) are intrinsic mediators of intercellular communication in our body, allowing functional transfer of biomolecules (lipids, proteins, and nucleic acid) between diverse locations. Such an instrumental role evokes a surge of interest within the drug delivery community in tailoring EVs for therapeutic delivery. These vesicles represent a novel generation of drug delivery systems, providing high delivery efficiency, intrinsic targeting properties, and low immunogenicity. In the recent years, considerable research efforts have been directed toward developing safe and efficient EV-based delivery vehicles...
July 21, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28739266/identification-of-%C3%AE-helix-4-%C3%AE-4-of-rab11a-as-a-novel-rab11-binding-domain-rbd-interaction-of-rab11a-with-the-prostacyclin-receptor
#10
Eamon P Mulvaney, Fergal O'Meara, Amir R Khan, David J O'Connell, B Therese Kinsella
The cellular trafficking of numerous G protein-coupled receptors (GPCRs) is known to be regulated by Rab proteins that involves a direct protein:protein interaction between the receptor and the GTPase. In the case of the human prostacyclin receptor (hIP), it undergoes agonist-induced internalization and subsequent Rab11a-dependent recyclization involving an interaction between a Rab11-binding domain (RBD) localized within its carboxyl-tail domain with Rab11a. However, the GPCR-interacting domain on Rab11a itself is unknown...
July 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28739256/palmitoylation-of-ca-2-channel-subunit-cav%C3%AE-2a-induces-pancreatic-beta-cell-toxicity-via-ca-2-overload
#11
Abdulla S Kazim, Petter Storm, Enming Zhang, Erik Renström
High blood glucose triggers the release of insulin from pancreatic beta cells, but if chronic, causes cellular stress, partly due to impaired Ca(2+) homeostasis. Ca(2+) influx is controlled by voltage-gated calcium channels (CaV) and high density of CaV in the plasma membrane could lead to Ca(2+) overload. Trafficking of the pore-forming CaVα1 subunit to the plasma membrane is regulated by auxiliary subunits, such as the CaVβ2a subunit. This study investigates, using Ca(2+) imaging and immunohistochemistry, the role of palmitoylation of CaVβ2a in maintaining Ca(2+) homeostasis and beta cell function...
July 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28738989/membrane-curvature-and-lipid-composition-synergize-to-regulate-n-ras-anchor-recruitment
#12
Jannik B Larsen, Celeste Kennard, Søren L Pedersen, Knud J Jensen, Mark J Uline, Nikos S Hatzakis, Dimitrios Stamou
Proteins anchored to membranes through covalently linked fatty acids and/or isoprenoid groups play crucial roles in all forms of life. Sorting and trafficking of lipidated proteins has traditionally been discussed in the context of partitioning to membrane domains of different lipid composition. We recently showed that membrane shape/curvature can in itself mediate the recruitment of lipidated proteins. However, exactly how membrane curvature and composition synergize remains largely unexplored. Here we investigated how three critical structural parameters of lipids, namely acyl chain saturation, headgroup size, and acyl chain length, modulate the capacity of membrane curvature to recruit lipidated proteins...
July 21, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28737243/investigating-the-genetic-regulation-of-the-expression-of-63-lipid-metabolism-genes-in-the-pig-skeletal-muscle
#13
R González-Prendes, R Quintanilla, M Amills
A comprehensive and systematic view of the genetic regulation of lipid metabolism genes is still lacking in pigs. Herewith, we have investigated the genetic regulation of 63 porcine genes with crucial roles in the uptake, transport, synthesis and catabolism of lipids. With this aim, we have performed an expression QTL (eQTL) scan in 104 pigs with available genotypes for the Illumina Porcine SNP60 chip and microarray measurements of gene expression in the gluteus medius muscle. Analysis of the data with gemma software revealed 13 cis- and 18 trans-eQTL modulating the expression of 19 loci...
July 24, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28736941/in-vivo-neutralization-of-%C3%AE-4-and-%C3%AE-7-integrins-inhibits-eosinophil-trafficking-and-prevents-lung-injury-during-tropical-pulmonary-eosinophilia-in-mice
#14
Pankaj Sharma, Aditi Sharma, Mrigank Srivastava
Integrins regulate leukocyte trafficking during homeostasis and inflammatory conditions. However, the role of α4 and β7 integrins in guiding eosinophil transmigration into the lungs during filarial manifestation of Tropical Pulmonary Eosinophilia (TPE) has not been explored. In this study, mice exhibiting TPE manifestations were administered with in vivo neutralizing antibodies against integrins α4 and β7 or their combination and immuno-pathological parameters were evaluated. Results show an intact lung barrier, significantly lower lung inflammation and reduced eosinophil counts in the Bronchoalveolar lavage fluid and lungs of mice receiving anti-α4(+) β7 treatment...
July 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28736525/pharmaceutical-chaperones-and-proteostasis-regulators-in-the-therapy-of-lysosomal-storage-disorders-current-perspective-and-future-promises
#15
REVIEW
Fedah E Mohamed, Lihadh Al-Gazali, Fatma Al-Jasmi, Bassam R Ali
Different approaches have been utilized or proposed for the treatment of lysosomal storage disorders (LSDs) including enzyme replacement and hematopoietic stem cell transplant therapies, both aiming to compensate for the enzymatic loss of the underlying mutated lysosomal enzymes. However, these approaches have their own limitations and therefore the vast majority of LSDs are either still untreatable or their treatments are inadequate. Missense mutations affecting enzyme stability, folding and cellular trafficking are common in LSDs resulting often in low protein half-life, premature degradation, aggregation and retention of the mutant proteins in the endoplasmic reticulum...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28735164/vesicle-trafficking-in-plant-immunity
#16
REVIEW
Hye Sup Yun, Chian Kwon
To defend against extracellular pathogens, plants primarily depend on cell-autonomous innate immunity due to the lack of the circulatory immune system including mobile immune cells. To extracellularly restrict or kill the pathogens, plant cells dump out antimicrobials. However, since antimicrobials are also toxic to plant cells themselves, they have to be safely delivered to the target sites in a separate vesicular compartment. In addition, because immune responses often requires energy otherwise used for the other metabolic processes, it is very important to properly control the duration and strength of immune responses depending on pathogen types...
July 20, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28734904/identifying-novel-members-of-the-wntless-interactome-through-genetic-and-candidate-gene-approaches
#17
Jessica Petko, Trevor Tranchina, Goral Patel, Robert Levenson, Stephanie Justice-Bitner
Wnt signaling is an important pathway that regulates several aspects of embryogenesis, stem cell maintenance, and neural connectivity. We have recently determined that opioids decrease Wnt secretion, presumably by inhibiting the recycling of the Wnt trafficking protein Wntless (Wls). This effect appears to be mediated by protein-protein interaction between Wls and the mu-opioid receptor (MOR), the primary cellular target of opioid drugs. The goal of this study was to identify novel protein interactors of Wls that are expressed in the brain and may also play a role in reward or addiction...
July 19, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28734845/leveraging-siglec-8-endocytic-mechanisms-to-kill-human-eosinophils-and-malignant-mast-cells
#18
Jeremy A O'Sullivan, Daniela J Carroll, Yun Cao, Adriano N Salicru, Bruce S Bochner
BACKGROUND: Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is a cell-surface protein expressed selectively on human eosinophils, mast cells, and basophils, making it an ideal target for the treatment of diseases involving these cell types. However, the effective delivery of therapeutic agents to these cells requires an understanding of the dynamics of Siglec-8 surface expression. OBJECTIVE: To determine whether Siglec-8 is endocytosed in human eosinophils and malignant mast cells, identify mechanisms underlying its endocytosis, and demonstrate whether a toxin can be targeted to Siglec-8-bearing cells to kill these cells...
July 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28734137/precision-targeting-by-phosphoinositides-how-pis-direct-endomembrane-trafficking-in-plants
#19
REVIEW
Lise C Noack, Yvon Jaillais
Each phosphoinositide (PI, also known as phosphatidylinositol phosphate, polyphosphoinositide, PtdInsP or PIP) species is partitioned in the endomembrane system and thereby contributes to the identity of membrane compartments. However, membranes are in constant flux within this system, which raises the questions of how the spatiotemporal pattern of phosphoinositides is established and maintained within the cell. Here, we review the general mechanisms by which phosphoinositides and membrane trafficking feedbacks on each other to regulate cellular patterning...
July 19, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28733327/cenp-a-and-topoisomerase-ii-antagonistically-affect-chromosome-length
#20
A-M Ladouceur, Rajesh Ranjan, Lydia Smith, Tanner Fadero, Jennifer Heppert, Bob Goldstein, Amy Shaub Maddox, Paul S Maddox
The size of mitotic chromosomes is coordinated with cell size in a manner dependent on nuclear trafficking. In this study, we conducted an RNA interference screen of the Caenorhabditis elegans nucleome in a strain carrying an exceptionally long chromosome and identified the centromere-specific histone H3 variant CENP-A and the DNA decatenizing enzyme topoisomerase-II (topo-II) as candidate modulators of chromosome size. In the holocentric organism C. elegans, CENP-A is positioned periodically along the entire length of chromosomes, and in mitosis, these genomic regions come together linearly to form the base of kinetochores...
July 21, 2017: Journal of Cell Biology
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