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https://www.readbyqxmd.com/read/29150528/autophagy-in-the-context-of-the-cellular-membrane-trafficking-system-the-enigma-of-atg9-vesicles
#1
REVIEW
Takeshi Noda
Macroautophagy is an intracellular degradation system that involves the de novo formation of membrane structures called autophagosomes, although the detailed process by which membrane lipids are supplied during autophagosome formation is yet to be elucidated. Macroautophagy is thought to be associated with canonical membrane trafficking, but several mechanistic details are still missing. In this review, the current understanding and potential mechanisms by which membrane trafficking participates in macroautophagy are described, with a focus on the enigma of the membrane protein Atg9, for which the proximal mechanisms determining its movement are disputable, despite its key role in autophagosome formation...
November 17, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29150077/unique-arginine-array-improves-cytosolic-localization-of-hydrocarbon-stapled-peptides
#2
Kim Quach, Jonathan LaRochelle, Xiao-Han Li, Elizabeth Rhoades, Alanna Schepartz
We have previously reported that miniature proteins containing a distinct array of 5 arginine residues on a folded α-helix - a penta-arg motif - traffic with high efficiency from endosomes into the cytosol and nucleus of mammalian cells. Here we evaluate whether a penta-arg motif can improve the intracellular trafficking of an otherwise impermeant hydrocarbon-stapled peptide, SAH-p53-4(Rho). We prepared a panel of SAH-p53-4(Rho) variants containing penta-arg sequences with different spacings and axial arrangement and evaluated their overall uptake (as judged by flow cytometry) and their intracellular access (as determined by fluorescence correlation spectroscopy, FCS)...
November 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29149845/early-nutritional-programming-affects-liver-transcriptome-in-diploid-and-triploid-atlantic-salmon-salmo-salar
#3
L M Vera, C Metochis, J F Taylor, M Clarkson, K H Skjærven, H Migaud, D R Tocher
BACKGROUND: To ensure sustainability of aquaculture, plant-based ingredients are being used in feeds to replace marine-derived products. However, plants contain secondary metabolites which can affect food intake and nutrient utilisation of fish. The application of nutritional stimuli during early development can induce long-term changes in animal physiology. Recently, we successfully used this approach to improve the utilisation of plant-based diets in diploid and triploid Atlantic salmon...
November 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29148969/the-structure-of-the-copi-coat-determined-within-the-cell
#4
Yury S Bykov, Miroslava Schaffer, Svetlana O Dodonova, Sahradha Albert, Jürgen M Plitzko, Wolfgang Baumeister, Benjamin D Engel, John Ag Briggs
COPI-coated vesicles mediate trafficking within the Golgi apparatus and from the Golgi to the endoplasmic reticulum. The structures of membrane protein coats, including COPI, have been extensively studied with in vitro reconstitution systems using purified components. In a previous paper (Dodonova et al., 2017), we determined a complete structural model of the in vitro reconstituted COPI coat. Here, we applied cryo-focused ion beam milling, cryo-electron tomography and subtomogram averaging to determine the native structure of the COPI coat within vitrified Chlamydomonas reinhardtii cells...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29146996/the-role-of-cxcr3-lrp1-cross-talk-in-the-invasion-of-primary-brain-tumors
#5
Kevin Boyé, Nadège Pujol, Isabel D Alves, Ya-Ping Chen, Thomas Daubon, Yi-Zong Lee, Stephane Dedieu, Marion Constantin, Lorenzo Bello, Marco Rossi, Rolf Bjerkvig, Shih-Che Sue, Andreas Bikfalvi, Clotilde Billottet
CXCR3 plays important roles in angiogenesis, inflammation, and cancer. However, the precise mechanism of regulation and activity in tumors is not well known. We focused on CXCR3-A conformation and on the mechanisms controlling its activity and trafficking and investigated the role of CXCR3/LRP1 cross talk in tumor cell invasion. Here we report that agonist stimulation induces an anisotropic response with conformational changes of CXCR3-A along its longitudinal axis. CXCR3-A is internalized via clathrin-coated vesicles and recycled by retrograde trafficking...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146937/tfeb-regulates-lysosomal-positioning-by-modulating-tmem55b-expression-and-jip4-recruitment-to-lysosomes
#6
Rose Willett, José A Martina, James P Zewe, Rachel Wills, Gerald R V Hammond, Rosa Puertollano
Lysosomal distribution is linked to the role of lysosomes in many cellular functions, including autophagosome degradation, cholesterol homeostasis, antigen presentation, and cell invasion. Alterations in lysosomal positioning contribute to different human pathologies, such as cancer, neurodegeneration, and lysosomal storage diseases. Here we report the identification of a novel mechanism of lysosomal trafficking regulation. We found that the lysosomal transmembrane protein TMEM55B recruits JIP4 to the lysosomal surface, inducing dynein-dependent transport of lysosomes toward the microtubules minus-end...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146912/structural-insights-into-legionella-ridl-vps29-retromer-subunit-interaction-reveal-displacement-of-the-regulator-tbc1d5
#7
Kevin Bärlocher, Cedric A J Hutter, A Leoni Swart, Bernhard Steiner, Amanda Welin, Michael Hohl, François Letourneur, Markus A Seeger, Hubert Hilbi
Legionella pneumophila can cause Legionnaires' disease and replicates intracellularly in a distinct Legionella-containing vacuole (LCV). LCV formation is a complex process that involves a plethora of type IV-secreted effector proteins. The effector RidL binds the Vps29 retromer subunit, blocks retrograde vesicle trafficking, and promotes intracellular bacterial replication. Here, we reveal that the 29-kDa N-terminal domain of RidL (RidL2-281) adopts a "foot-like" fold comprising a protruding β-hairpin at its "heel"...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146731/organic-anion-transporting-polypeptide-1b3-as-a-dual-reporter-gene-for-fluorescence-and-magnetic-resonance-imaging
#8
Menq-Rong Wu, Hon-Man Liu, Chen-Wen Lu, Way-Hone Shen, I-Jou Lin, Li-Wen Liao, Yi-You Huang, Ming-Jium Shieh, Jong-Kai Hsiao
Reporter proteins have broad applications in visualizing molecular events at the cellular, tissue and whole-body levels. Transmembrane transporters recognizing specific molecular domains are of particular interest because they enable the migration of signal-source molecules from the extracellular space to the cytoplasm for subsequent application in multimodality imaging. Organic anion-transporting polypeptides (OATPs) have demonstrated their MRI reporter efficacy. We further expanded their use as a dual-modality reporter in MRI and noninvasive in vivo imaging system (IVIS)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146245/repurposing-cationic-amphiphilic-drugs-as-adjuvants-to-induce-lysosomal-sirna-escape-in-nanogel-transfected-cells
#9
Freya Joris, Lynn De Backer, Thijs Van de Vyver, Chiara Bastiancich, Stefaan C De Smedt, Koen Raemdonck
Cytosolic delivery remains a major bottleneck for siRNA therapeutics. To facilitate delivery, siRNAs are often enclosed in nanoparticles (NPs). However, upon endocytosis such NPs are mainly trafficked towards lysosomes. To avoid degradation, cytosolic release of siRNA should occur prior to fusion of endosomes with lysosomes, but current endosomal escape strategies remain inefficient. In contrast to this paradigm, we aim to exploit lysosomal accumulation by treating NP-transfected cells with low molecular weight drugs that release the siRNA from the lysosomes into the cytosol...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29146226/the-n-terminal-domains-of-bacillus-subtilis-copa-do-not-form-a-stable-complex-in-the-absence-of-their-inter-domain-linker
#10
Liang Zhou, Kristine L Kay, Oliver Hecht, Geoffrey R Moore, Nick E Le Brun
Copper-transporting P-type ATPases, which play important roles in trafficking Cu(I) across membranes for the biogenesis of copper proteins or for copper detoxification, contain a variable number of soluble metal-binding domains at their N-termini. It is increasingly apparent that these play an important role in regulating copper transport in a Cu(I)-responsive manner, but how they do this is unknown. CopA, a Cu(I)-transporter from Bacillus subtilis, contains two N-terminal soluble domains that are closely packed, with inter-domain interactions at two principal regions...
November 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29146210/novel-intracellular-transport-refractory-mutations-in-kcnh2-identified-in-patients-with-symptomatic-long-qt-syndrome
#11
Daisuke Fukumoto, Wei-Guang Ding, Yuko Wada, Yusuke Fujii, Mari Ichikawa, Koichiro Takayama, Megumi Fukuyama, Koichi Kato, Hideki Itoh, Takeru Makiyama, Mariko Omatsu-Kanbe, Hiroshi Matsuura, Minoru Horie, Seiko Ohno
BACKGROUND: Missense mutations in KCNH2, a gene encoding the Kv11.1 channel, cause long QT syndrome (LQTS) type 2 primarily by disrupting the intracellular transport of Kv11.1 to the plasma membrane. The present study aimed to clarify the functional changes by two novel KCNH2 missense mutations. METHODS: We performed genetic screening of three unrelated symptomatic LQTS probands with family histories of cardiac symptoms. Chinese hamster ovary cells were transfected with wild-type (WT) and/or mutant KCNH2 plasmid and examined by patch-clamp technique...
November 13, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/29145888/tgf-%C3%AE-2-initiates-autophagy-via-smad-and-non-smad-pathway-to-promote-glioma-cells-invasion
#12
Chao Zhang, Xin Zhang, Ran Xu, Bin Huang, An-Jing Chen, Chao Li, Jian Wang, Xin-Gang Li
BACKGROUND: Glioblastoma multiforme (GBM) is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focused on roles of cytokines in tumor microenvironment and numerous evidence suggests that TGF-β2 is abundant in glioma microenvironment and vital for glioma invasion. Autopagy is also emerging as a critical factor in aggressive behaviors of cancer cells; however, the relationship between TGF-β2 and autophagy in glioma has been poorly understood...
November 16, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29145394/unc-16-jip3-regulates-early-events-in-synaptic-vesicle-protein-trafficking-via-lrk-1-lrrk2-and-ap-complexes
#13
Bikash Choudhary, Madhushree Kamak, Neena Ratnakaran, Jitendra Kumar, Anjali Awasthi, Chun Li, Ken Nguyen, Kunihiro Matsumoto, Naoki Hisamoto, Sandhya P Koushika
JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the μ-subunit of the AP-1 complex...
November 16, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29145048/development-of-a-microscale-land-use-regression-model-for-predicting-no2-concentrations-at-a-heavy-trafficked-suburban-area-in-auckland-nz
#14
L F Weissert, J A Salmond, G Miskell, M Alavi-Shoshtari, D E Williams
Land use regression (LUR) analysis has become a key method to explain air pollutant concentrations at unmeasured sites at city or country scales, but little is known about the applicability of LUR at microscales. We present a microscale LUR model developed for a heavy trafficked section of road in Auckland, New Zealand. We also test the within-city transferability of LUR models developed at different spatial scales (local scale and city scale). Nitrogen dioxide (NO2) was measured during summer at 40 sites and a LUR model was developed based on standard criteria...
November 13, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29144986/decadal-changes-in-emissions-of-volatile-organic-compounds-vocs-from-on-road-vehicles-with-intensified-automobile-pollution-control-case-study-in-a-busy-urban-tunnel-in-south-china
#15
Yanli Zhang, Weiqiang Yang, Isobel Simpson, Xinyu Huang, Jianzhen Yu, Zhonghui Huang, Zhaoyi Wang, Zhou Zhang, Di Liu, Zuzhao Huang, Yujun Wang, Chenglei Pei, Min Shao, Donald R Blake, Junyu Zheng, Zhijiong Huang, Xinming Wang
In the efforts at controlling automobile emissions, it is important to know in what extent air pollutants from on-road vehicles could be truly reduced. In 2014 we conducted tests in a heavily trafficked tunnel in south China to characterize emissions of volatile organic compounds (VOC) from on-road vehicle fleet and compared our results with those obtained in the same tunnel in 2004. Alkanes, aromatics, and alkenes had average emission factors (EFs) of 338, 63, and 42 mg km(-1) in 2014 against that of 194, 129, and 160 mg km(-1) in 2004, respectively...
November 13, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29143559/k-cl-co-transporter-2-kcc2-a-membrane-trafficking-perspective
#16
Bor Luen Tang
K(+)-Cl(-) co-transporter 2 (KCC2/SLC12A5) is a neuronal specific cation chloride co-transporter which is active under isotonic conditions, and thus a key regulator of intracellular Cl(-) levels. It also has an ion transporter-independent structural role in modulating the maturation and regulation of excitatory glutamatergic synapses. KCC2 levels are developmentally regulated, and a postnatal upregulation of KCC2 generates a low intracellular chloride concentration that allows the neurotransmitters γ-aminobutyric acid (GABA) and glycine to exert inhibitory neurotransmission through its Cl(-) permeating channel...
November 16, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/29143554/the-octanoylated-energy-regulating-hormone-ghrelin-an-expanded-view-of-ghrelin-s-biological-interactions-and-avenues-for-controlling-ghrelin-signaling
#17
Elizabeth R Cleverdon, Kayleigh R McGovern-Gooch, James L Hougland
Ghrelin is a small peptide hormone that requires a unique post-translational modification, serine octanoylation, to bind and activate the GHS-R1a receptor. Initially demonstrated to stimulate hunger and appetite, ghrelin-dependent signaling is implicated in a variety of neurological and physiological processes influencing diseases such as diabetes, obesity, and Prader-Willi syndrome. In addition to its cognate receptor, recent studies have revealed ghrelin interacts with a range of binding partners within the bloodstream...
November 16, 2017: Molecular Membrane Biology
https://www.readbyqxmd.com/read/29142285/blockade-of-cb1-cannabinoid-receptor-alters-gut-microbiota-and-attenuates-inflammation-and-diet-induced-obesity
#18
Pegah Mehrpouya-Bahrami, Kumaraswamy Naidu Chitrala, Mitra S Ganewatta, Chuanbing Tang, E Angela Murphy, Reilly T Enos, Kandy T Velazquez, Jamie McCellan, Mitzi Nagarkatti, Prakash Nagarkatti
Obesity is characterized by chronic low-grade, systemic inflammation, altered gut microbiota, and gut barrier disruption. Additionally, obesity is associated with increased activity of endocannabinoid system (eCB). However, the clear connection between gut microbiota and the eCB system in the regulation of energy homeostasis and adipose tissue inflammation and metabolism, remains to be established. We investigated the effect of treatment of mice with a cannabinoid receptor 1 (CB1) antagonist on Diet-Induced Obesity (DIO), specifically whether such a treatment that blocks endocannabinoid activity can induce changes in gut microbiota and anti-inflammatory state in adipose tissue...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142232/tdp-43-misexpression-causes-defects-in-dendritic-growth
#19
Josiah J Herzog, Mugdha Deshpande, Leah Shapiro, Avital A Rodal, Suzanne Paradis
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) share overlapping genetic causes and disease symptoms, and are linked neuropathologically by the RNA binding protein TDP-43 (TAR DNA binding protein-43 kDa). TDP-43 regulates RNA metabolism, trafficking, and localization of thousands of target genes. However, the cellular and molecular mechanisms by which dysfunction of TDP-43 contributes to disease pathogenesis and progression remain unclear. Severe changes in the structure of neuronal dendritic arbors disrupt proper circuit connectivity, which in turn could contribute to neurodegenerative disease...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142197/proteotoxicity-in-cardiac-amyloidosis-amyloidogenic-light-chains-affect-the-levels-of-intracellular-proteins-in-human-heart-cells
#20
Esther Imperlini, Massimiliano Gnecchi, Paola Rognoni, Eduard Sabidò, Maria Chiara Ciuffreda, Giovanni Palladini, Guadalupe Espadas, Francesco Mattia Mancuso, Margherita Bozzola, Giuseppe Malpasso, Veronica Valentini, Giuseppina Palladini, Stefania Orrù, Giovanni Ferraro, Paolo Milani, Stefano Perlini, Francesco Salvatore, Giampaolo Merlini, Francesca Lavatelli
AL amyloidosis is characterized by widespread deposition of immunoglobulin light chains (LCs) as amyloid fibrils. Cardiac involvement is frequent and leads to life-threatening cardiomyopathy. Besides the tissue alteration caused by fibrils, clinical and experimental evidence indicates that cardiac damage is also caused by proteotoxicity of prefibrillar amyloidogenic species. As in other amyloidoses, the damage mechanisms at cellular level are complex and largely undefined. We have characterized the molecular changes in primary human cardiac fibroblasts (hCFs) exposed in vitro to soluble amyloidogenic cardiotoxic LCs from AL cardiomyopathy patients...
November 15, 2017: Scientific Reports
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