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https://www.readbyqxmd.com/read/27907003/mapping-cholesterol-interaction-sites-on-serotonin-transporter-through-coarse-grained-molecular-dynamics
#1
Mariarosaria Ferraro, Matteo Masetti, Maurizio Recanatini, Andrea Cavalli, Giovanni Bottegoni
Serotonin transporter (SERT) modulates serotonergic signaling via re-uptake of serotonin in pre-synaptic cells. The inclusion in cholesterol-enriched membrane domains is crucial for SERT activity, suggesting a cross-talk between the protein and the sterol. Here, we develop a protocol to identify potential cholesterol interaction sites coupling statistical analysis to multi-microsecond coarse-grained molecular dynamics simulations of SERT in a previously validated raft-like membrane model. Six putative sites were found, including a putative CRAC motif on TM4 and a CARC motif on TM10...
2016: PloS One
https://www.readbyqxmd.com/read/27899526/dynamic-pre-bcr-homodimers-fine-tune-autonomous-survival-signals-in-b-cell-precursor-acute-lymphoblastic-leukemia
#2
M Frank Erasmus, Ksenia Matlawska-Wasowska, Ichiko Kinjyo, Avanika Mahajan, Stuart S Winter, Li Xu, Michael Horowitz, Diane S Lidke, Bridget S Wilson
The pre-B cell receptor (pre-BCR) is an immature form of the BCR critical for early B lymphocyte development. It is composed of the membrane-bound immunoglobulin (Ig) heavy chain, surrogate light chain components, and the signaling subunits Igα and Igβ. We developed monovalent quantum dot (QD)-labeled probes specific for Igβ to study the behavior of pre-BCRs engaged in autonomous, ligand-independent signaling in live B cells. Single-particle tracking revealed that QD-labeled pre-BCRs engaged in transient, but frequent, homotypic interactions...
November 29, 2016: Science Signaling
https://www.readbyqxmd.com/read/27895118/co-evolution-of-two-gtpases-enables-efficient-protein-targeting-in-an-rna-less-chloroplast-signal-recognition-particle-pathway
#3
Sowmya Chandrasekar, Michael J Sweredoski, Chang Ho Sohn, Sonja Hess, Shu-Ou Shan
Signal Recognition Particle (SRP) is an essential ribonucleoprotein particle that mediates the co-translational targeting of newly synthesized proteins to cellular membranes. The SRP RNA is a universally conserved component of SRP that mediates key interactions between two GTPases in SRP and its receptor, and thus enables rapid delivery of cargo to the target membrane. Notably, this essential RNA is bypassed in the chloroplast SRP (cpSRP) of green plants. Previously, we showed that the cpSRP and cpSRP receptor GTPases (cpSRP54 and cpFtsY, respectively) could interact efficiently by themselves without the SRP RNA...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27876895/multiple-crosstalk-between-tor-and-the-cell-integrity-mapk-signaling-pathway-in-fission-yeast
#4
Marisa Madrid, Beatriz Vázquez-Marín, Alejandro Franco, Teresa Soto, Jero Vicente-Soler, Mariano Gacto, José Cansado
In eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive responses to extra- and intracellular conditions by regulating essential cellular functions. However, the nature of the functional relationships between both pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall structure and ionic homeostasis. We show that the Rab GTPase Ryh1, a TORC2 complex activator, cross-activates the CIP and its core member, the MAPK Pmk1, by two distinct mechanisms...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27866075/bioaccumulation-and-subcellular-partitioning-of-cr-iii-and-cr-vi-in-the-freshwater-green-alga-chlamydomonas-reinhardtii
#5
Imad Aharchaou, Maikel Rosabal, Fengjie Liu, Eric Battaglia, Davide A L Vignati, Claude Fortin
Chromium occurs in aquatic environments under two main redox forms, namely Cr(III) and Cr(VI), with different geochemical and biochemical properties. Cr(VI) readily crosses biological membranes of living organisms and once inside the cells it undergoes a rapid reduction to Cr(III). The route of entry for the latter form is, however, poorly known. Using the radioactive tracer (51)Cr we compared the accumulation (absorption and adsorption) of the two Cr forms by the green unicellular alga Chlamydomonas reinhardii after 1h and 72h of exposure to 100nM of either Cr(III) or Cr(VI) at pH 7...
November 6, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27847330/altered-mitochondrial-quality-control-signaling-in-muscle-of-old-gastric-cancer-patients-with-cachexia
#6
Emanuele Marzetti, Maria Lorenzi, Francesco Landi, Anna Picca, Fausto Rosa, Fabiana Tanganelli, Marco Galli, Giovanni Battista Doglietto, Fabio Pacelli, Matteo Cesari, Roberto Bernabei, Riccardo Calvani, Maurizio Bossola
Mitochondrial dysfunction is involved in the loss of muscle featuring both aging and cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes of old patients with CC is unclear. The present investigation therefore sought to preliminarily characterize MQC pathways in muscle of old gastric cancer patients with cachexia. The study followed a case-control cross-sectional design. Intraoperative biopsies of the rectus abdominis muscle were obtained from 18 patients with gastric adenocarcinoma (nine with CC and nine non-cachectic) and nine controls, and assayed for the expression of a set of MQC mediators...
November 12, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27824087/trafficking-of-the-exported-p-falciparum-chaperone-pfhsp70x
#7
Manuel Rhiel, Verena Bittl, Anke Tribensky, Sarah C Charnaud, Maja Strecker, Sebastian Müller, Michael Lanzer, Cecilia Sanchez, Christine Schaeffer-Reiss, Benoit Westermann, Brendan S Crabb, Paul R Gilson, Simone Külzer, Jude M Przyborski
Plasmodium falciparum extensively modifies its chosen host cell, the mature human erythrocyte. This remodelling is carried out by parasite-encoded proteins that are exported into the host cell. To gain access to the human red blood cell, these proteins must cross the parasitophorous vacuole, a membrane bound compartment surrounding the parasite that is generated during the invasion process. Many exported proteins carry a so-called PEXEL/HT signal that directs their transport. We recently reported the unexpected finding of a species-restricted parasite-encoded Hsp70, termed PfHsp70x, which is exported into the host erythrocyte cytosol...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27809400/structural-analysis-of-endothelial-projections-from-mesenteric-arteries
#8
Nadia Maarouf, Maria Sancho, Tobias Fürstenhaupt, Cam Ha Tran, Donald G Welsh
OBJECTIVE: Endothelial and smooth muscle cells must communicate with one another to regulate arterial diameter. A key structure driving heterocellular communication is the endothelial projection, a thin extension that crosses the internal elastic lamina (IEL) making contact with smooth muscle. This study sought to define the precise structural composition of endothelial projections in the mesenteric circulation. METHODS: Third and fourth order mesenteric arteries from hamster were prepared for electron microscopy...
November 3, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/27799936/ectopic-expression-of-jcwrky-transcription-factor-confers-salinity-tolerance-via-salicylic-acid-signaling
#9
Parinita Agarwal, Mitali Dabi, Komal K Sapara, Priyanka S Joshi, Pradeep K Agarwal
Plants, being sessile, have developed intricate signaling network to specifically respond to the diverse environmental stress. The plant-specific WRKY TFs form one of the largest TF family and are involved in diverse plant processes, involving growth, development and stress signaling through auto and cross regulation with different genes and TFs. Here, we report the functional characterization of a salicylic acid -inducible JcWRKY TF. The JcWRKY overexpression confers salinity tolerance in transgenic tobacco, as was evident by increased chlorophyll content and seed germination potential...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27799031/calcium-calpain-dependent-pathways-regulate-vesiculation-in-malignant-breast-cells
#10
Jack Taylor, Ritu Jaiswal, Mary Bebawy
Multidrug resistance in cancer (MDR) occurs when tumours become cross-resistant to a range of different anticancer agents. One mechanism by which MDR can be acquired is through cell to cell communication pathways. Membrane-derived microparticles (MPs) are emerging as important signaling molecules in this process. MPs are released from most eukaryotic cells and transfer functional proteins and nucleic acids to recipient cells conferring deleterious traits within the cancer cell population including MDR, metastasis, and angiogenesis...
October 26, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27798864/inhibition-of-galectin-1-sensitizes-hras-driven-tumor-growth-to-rapamycin-treatment
#11
James V Michael, Jeremy G T Wurtzel, Lawrence E Goldfinger
The goal of this study was to develop combinatorial application of two drugs currently either in active use as anticancer agents (rapamycin) or in clinical trials (OTX008) as a novel strategy to inhibit Harvey RAS (HRAS)-driven tumor progression. HRAS anchored to the plasma membrane shuttles from the lipid ordered (Lo) domain to the lipid ordered/lipid disordered border upon activation, and retention of HRAS at these sites requires galectin-1. We recently showed that genetically enforced Lo sequestration of HRAS inhibited mitogen-activated protein kinase (MAPK) signaling, but not phoshatidylinositol 3-kinase (PI3K) activation...
October 2016: Anticancer Research
https://www.readbyqxmd.com/read/27795355/snap23-dependent-surface-translocation-of-blt1-is-essential-for-nox2-mediated-exocytotic-degranulation-in-human-mast-cells-induced-by-trichomonas-vaginalis-secreted-ltb4
#12
Arim Min, Young Ah Lee, Kyeong Ah Kim, Jamel El-Benna, Myeong Heon Shin
Trichomonas vaginalis is a sexually transmitted parasite that causes vaginitis in women and itself secretes lipid mediator LTB4 Mast cells are important effector cells of tissue inflammation during infection with parasites. Membrane-bridging SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) complexes are critical for fusion during exocytosis. Although T. vaginalis-derived secretory products (TvSP) have been shown to induce exocytosis in mast cells, information regarding the signaling mechanisms between mast cell activation and TvSP is limited...
October 24, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27794298/finite-element-modelling-of-cochlear-electrical-coupling
#13
Paul D Teal, Guangjian Ni
The operation of each hair cell within the cochlea generates a change in electrical potential at the frequency of the vibrating basilar membrane beneath the hair cell. This electrical potential influences the operation of the cochlea at nearby locations and can also be detected as the cochlear microphonic signal. The effect of such potentials has been proposed as a mechanism for the non-local operation of the cochlear amplifier, and the interaction of such potentials has been thought to be the cause of the broadness of cochlea microphonic tuning curves...
October 2016: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/27761756/tissue-transglutaminase-tg2-is-involved-in-the-resistance-of-cancer-cells-to-the-histone-deacetylase-hdac-inhibitor-vorinostat
#14
Carmine Carbone, Elena Di Gennaro, Geny Piro, Maria Rita Milone, Biagio Pucci, Michele Caraglia, Alfredo Budillon
Vorinostat demonstrated preclinical and clinical efficacy in human cancers and is the first histone deacetylase inhibitor (HDACi) approved for cancer treatment. Tissue transglutaminase (TG2) is a multifunctional enzyme that catalyzes a Ca(2+) dependent transamidating reaction resulting in covalent cross-links between proteins. TG2 acts also as G-protein in trans-membrane signaling and as a cell surface adhesion mediator. TG2 up-regulation has been demonstrated in several cancers and its expression levels correlate with resistance to chemotherapy and metastatic potential...
October 19, 2016: Amino Acids
https://www.readbyqxmd.com/read/27754302/lbos-02-03-the-infiltrating-macrophage-secreted-galectin-3-plays-an-essential-role-in-cardiac-fibrosis-and-diastolic-function-in-murine-pressure-overload-model
#15
Jin-Jer Chen, Wen-Rui Hao, Kuan-Cheng Chang, Ju-Chi Liu
OBJECTIVE: Cardiac fibrosis is the major pathophysiological process, contributing to the development of diastolic heart failure. We examine the role of macrophage-derived galectin-3 (gal-3) in cardiac fibrosis and diastolic function in response to transverse aortic constriction (TAC). DESIGN AND METHOD: wild-type (WT) and gal-3 knock-out (KO) mice subjected to TAC; immunohistochemistry for myocardial macrophage infiltration,gal-3,and CTGF (connective tissue growth factor) expression; picrosirius red stain for myocardial fibrosis; FACS flow- cytometry for defining the origin of myocardial macrophages...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27748602/molecular-level-interactions-of-polyphosphazene-immunoadjuvants-and-their-potential-role-in-antigen-presentation-and-cell-stimulation
#16
Alexander K Andrianov, Alexander Marin, Thomas R Fuerst
Two macromolecular immunoadjuvants - poly[di(carboxylatophenoxy)phosphazene], PCPP and poly[di(carboxylatoethylphenoxy)phosphazene], PCEP have been investigated for their molecular interactions with model and bio-pharmaceutically important proteins in solutions, as well as for their TLR stimulatory effects and pH-dependent membrane disruptive activity in cellular assays. Solution interactions between polyphosphazenes and proteins, including antigens and soluble immune receptor proteins, have been studied using Asymmetric Flow Field Flow Fractionation (AF4) and Dynamic Light Scattering (DLS) at near physiological conditions - phosphate buffered saline, pH 7...
October 17, 2016: Biomacromolecules
https://www.readbyqxmd.com/read/27737648/interplay-of-n-cadherin-and-matrix-metalloproteinase-9-enhances-human-nasopharyngeal-carcinoma-cell-invasion
#17
Chih-Chin Hsu, Shiang-Fu Huang, Jong-Shyan Wang, Wing-Keung Chu, Ju-En Nien, Wei-Shan Chen, Shu-Er Chow
BACKGROUND: N-cadherin is a trans-membrane adhesion molecule associated with advanced carcinoma progression and poor prognosis. The effect of N-cadherin on matrix metalloproteinase 9 (MMP-9) regulation is implicated in human nasopharyngeal carcinoma (NPC) cell invasion. METHODS AND RESULTS: Exposure of NPC cells to phorbol-12-myristate-13-acetate (PMA) or macrophage conditioned media (CM) upregulated MMP-9 and N-cadherin cleavage, which resulted in NPC cell invasion...
October 13, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27734193/effect-of-a-flexible-linker-on-recombinant-expression-of-cell-penetrating-peptide-fusion-proteins-and-their-translocation-into-fungal-cells
#18
Zifan Gong, Mackenzie T Walls, Alisha N Karley, Amy J Karlsson
Cell-penetrating peptides (CPPs) are a class of small peptides that are able to cross cell membranes via direct translocation or endocytosis. They have been widely used to deliver tethered bioactive molecules to cells, but recombinantly producing CPPs as fusions to protein cargo leads to low yields. We used Escherichia coli cells to recombinantly produce genetic fusions of NPFSD (derived from a yeast endocytosis signal) and pVEC (derived from a murine vascular endothelium cadherin) to the N-terminus of green fluorescent protein (GFP) with and without a flexible glycine-serine linker between the CPP and GFP...
October 12, 2016: Molecular Biotechnology
https://www.readbyqxmd.com/read/27732950/specificity-and-biologic-activities-of-novel-anti-membrane-igm-antibodies
#19
Rachel S Welt, Jonathan A Welt, David Kostyal, Yamuna D Gangadharan, Virginia Raymond, Sydney Welt
The concept that the B-cell Receptor (BCR) initiates a driver pathway in lymphoma-leukemia has been clinically validated. Previously described unique BCR Ig-class-specific sequences (proximal domains (PDs)), are not expressed in serum Ig (sIg). As a consequence of sequence and structural differences in the membrane IgM (mIgM) µ-Constant Domain 4, additional epitopes distinguish mIgM from sIgM. mAbs generated to linear and conformational epitopes, restricted to mIgM and not reacting with sIgM, were generated despite the relative hydrophobicity of the PDm sequence...
October 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27724860/testis-specific-gtpase-tsg-an-oligomeric-protein
#20
Sudeep Kumar, Hyun Joo Lee, Hee-Sae Park, Keesook Lee
BACKGROUND: Ras-related proteins in brain (Rab)-family proteins are key members of the membrane trafficking pathway in cells. In addition, these proteins have been identified to have diverse functions such as cross-talking with different kinases and playing a role in cellular signaling. However, only a few Rab proteins have been found to have a role in male germ cell development. The most notable functions of this process are performed by numerous testis-specific and/or germ cell-specific genes...
October 10, 2016: BMC Genomics
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