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https://www.readbyqxmd.com/read/27909244/cd4-down-regulation-by-hiv-1-nef-reveals-distinct-roles-for-%C3%AE-1-and-%C3%AE-2-subunits-of-ap-1-complex-in-protein-trafficking
#1
Lucas A Tavares, Eulália M L da Silva, Mara E da Silva-Januário, Yunan C Januário, Julianne V de Cavalho, Érika S Czernisz, Gonzalo A Mardones, Luis L P daSilva
The HIV accessory protein Nef is a major determinant of viral pathogenesis that facilitates viral particle release, prevents viral antigen presentation and increases infectivity of new virus particles. These functions of Nef involve its ability to remove specific host proteins from the surface of infected cells, including the CD4 receptor. Nef binds to the adaptor protein 2 (AP-2) and CD4 in clathrin-coated pits, forcing CD4 internalization and subsequent target to lysosomes. Herein, we report that this lysosomal targeting requires a variant of the AP-1 comprising the isoform 2 of γ-adaptin...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27829368/tfap-2-is-required-for-night-sleep-in-drosophila
#2
Mariya M Kucherenko, Vinodh Ilangovan, Bettina Herzig, Halyna R Shcherbata, Henrik Bringmann
BACKGROUND: The AP-2 transcription factor APTF-1 is crucially required for developmentally controlled sleep behavior in Caenorhabditis elegans larvae. Its human ortholog, TFAP-2beta, causes Char disease and has also been linked to sleep disorders. These data suggest that AP-2 transcription factors may be highly conserved regulators of various types of sleep behavior. Here, we tested the idea that AP-2 controls adult sleep in Drosophila. RESULTS: Drosophila has one AP-2 ortholog called TfAP-2, which is essential for viability...
November 9, 2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27809943/use-of-molecular-biomarkers-to-estimate-manganese-requirements-for-broiler-chickens-from-22-to-42-d-of-age
#3
Lin Lu, Bin Chang, Xiudong Liao, Runlian Wang, Liyang Zhang, Xugang Luo
The present study was carried out to evaluate dietary Mn requirements of broilers from 22 to 42 d of age using molecular biomarkers. Chickens were fed a conventional basal maize-soyabean meal diet supplemented with Mn as Mn sulphate in graded concentrations of 20 mg Mn/kg from 0 to 140 mg Mn/kg of diet for 21 d (from 22 to 42 d of age). The Mn response curves were fitted for ten parameters including heart Mn-containing superoxide dismutase (MnSOD) mRNA and its protein expression levels and the DNA-binding activities of specificity protein 1 (Sp1) and activating protein-2 (AP-2)...
November 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27799303/different-doublecortin-dcx-patient-alleles-show-distinct-phenotypes-in-cultured-neurons-evidence-for-divergent-loss-of-function-and-off-pathway-cellular-mechanisms
#4
Chan Choo Yap, Laura Digilio, Lloyd McMahon, Matylda Roszkowska, Christopher J Bott, Kamil Kruczek, Bettina Winckler
DCX (doublecortin on the X-chromosome) is a neuronal microtubule-binding protein with a multitude of roles in neurodevelopment. In humans, DCX is a major genetic locus for X-linked lissencephaly. The best-studied defects are in neuronal migration during corticogenesis and in the hippocampus, as well as axon and dendrite growth defects. Much effort has been directed at understanding the molecular and cellular bases of DCX-linked lissencephaly. The focus has been in particular on defects in microtubule assembly and bundling, using knock-out mice and expression of WT and mutant DCX in non-neuronal cells...
October 31, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27769893/phenylethanolamine-n-methyltransferase-gene-expression-in-adrenergic-neurons-of-spontaneously-hypertensive-rats
#5
Julie Grandbois, Sandhya Khurana, Kelly Graff, Phong Nguyen, Leah Meltz, T C Tai
Epinephrine is synthesised by the catecholamine biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT), primarily in chromaffin cells of the adrenal medulla and secondarily in brainstem adrenergic neurons of the medulla oblongata. Epinephrine is an important neurotransmitter/neurohormone involved in cardiovascular regulation; however, overproduction is detrimental with negative outcomes such as cellular damage, cardiovascular dysfunction, and hypertension. Genetic mapping studies have linked elevated expression of PNMT to hypertension...
December 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27698912/mir-193a-5p-targets-the-coding-region-of-ap-2%C3%AE-mrna-and-induces-cisplatin-resistance-in-bladder-cancers
#6
Ji Zhou, Huaxin Duan, Yu Xie, Yichong Ning, Xing Zhang, Na Hui, Chunqing Wang, Jian Zhang, Jianlin Zhou
Transcription factor AP-2 alpha (AP-2α or TFAP2A) is a newly identified prognostic marker of chemotherapy; its expression is positively correlated with chemosensitivity and survival of cancer patients. Using computational programs, we predicted that the coding region of AP-2α gene contains a potential miRNA response element (MRE) of miR-193a-5p, and the single nucleotide polymorphism (SNP) site (c.497A>G, rs111681798) resides within the predicted MRE. The results of luciferase assays and Western blot analysis demonstrated that miR-193a-5p negatively regulated the expression of AP-2α proteins, but have no influence on the mutant AP-2α (c...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27670116/npf-motifs-in-the-vaccinia-virus-protein-a36-recruit-intersectin-1-to-promote-cdc42-n-wasp-mediated-viral-release-from-infected-cells
#7
Xenia Snetkov, Ina Weisswange, Julia Pfanzelter, Ashley C Humphries, Michael Way
During its egress, vaccinia virus transiently recruits AP-2 and clathrin after fusion with the plasma membrane. This recruitment polarizes the viral protein A36 beneath the virus, enhancing actin polymerization and the spread of infection. We now demonstrate that three NPF motifs in the C-terminus of A36 recruit AP-2 and clathrin by interacting directly with the Epsin15 homology domains of Eps15 and intersectin-1. A36 is the first identified viral NPF motif containing protein shown to interact with endocytic machinery...
2016: Nature Microbiology
https://www.readbyqxmd.com/read/27650546/cogaps-matrix-factorization-algorithm-identifies-transcriptional-changes-in-ap-2alpha-target-genes-in-feedback-from-therapeutic-inhibition-of-the-egfr-network
#8
Elana J Fertig, Hiroyuki Ozawa, Manjusha Thakar, Jason D Howard, Luciane T Kagohara, Gabriel Krigsfeld, Ruchira S Ranaweera, Robert M Hughes, Jimena Perez, Siân Jones, Alexander V Favorov, Jacob Carey, Genevieve Stein-O'Brien, Daria A Gaykalova, Michael F Ochs, Christine H Chung
Patients with oncogene driven tumors are treated with targeted therapeutics including EGFR inhibitors. Genomic data from The Cancer Genome Atlas (TCGA) demonstrates molecular alterations to EGFR, MAPK, and PI3K pathways in previously untreated tumors. Therefore, this study uses bioinformatics algorithms to delineate interactions resulting from EGFR inhibitor use in cancer cells with these genetic alterations. We modify the HaCaT keratinocyte cell line model to simulate cancer cells with constitutive activation of EGFR, HRAS, and PI3K in a controlled genetic background...
September 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27605582/chronic-insulin-treatment-phosphorylates-the-renal-na-k-atpase-%C3%AE-1-subunit-at-serine-16-23-and-reduces-its-activity-involving-pi3-kinase-dependent-pkc-activation
#9
Anees Ahmad Banday
The regulation of Na-K-ATPase in various tissues is under the control of a number of hormones and peptides that exert both short- and long-term control over its activity. The present study was performed to investigate the effect of chronic insulin treatment on Na-K-ATPase in renal proximal tubular cells. Incubation of opossum kidney (OK) cells, transfected with the rat Na-K-ATPase α1-subunit, with 1 nmol/l insulin for 48 h decreased Na-K-ATPase activity. Insulin decreased α1-protein content and increased α1-serine phosphorylation and α1-adaptor protein 2 (AP2) interaction...
November 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27587839/atg9a-trafficking-through-the-recycling-endosomes-is-required-for-autophagosome-formation
#10
Kenta Imai, Feike Hao, Naonobu Fujita, Yasuhiro Tsuji, Yukako Oe, Yasuhiro Araki, Maho Hamasaki, Takeshi Noda, Tamotsu Yoshimori
Autophagy is an intracellular degradation pathway conserved in eukaryotes. Among core autophagy-related (Atg) proteins, mammalian Atg9A is the sole multi-spanning transmembrane protein, and both of its N- and C-terminal domains are exposed to the cytoplasm. It is known that Atg9A travels through the trans-Golgi network (TGN) and the endosomal system under nutrient-rich conditions, and transiently localizes to the autophagosome upon autophagy induction. However, the significance of Atg9A trafficking for autophagosome formation remains elusive...
October 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27565982/detection-of-four-polymorphisms-in-5-upstream-region-of-pnpla2-gene-and-their-associations-with-economic-traits-in-pigs
#11
Lihe Dai, Xiaohong Chu, Fuzeng Lu, Ruhai Xu
As an important triglyceride hydrolase in mammalian cells, patatin-like phospholipase domain-containing 2 (PNPLA2) predominantly performs the first step in triglyceride hydrolysis. The objective of this study was to detect and evaluate the effects of mutations in the 5' upstream region of porcine PNPLA2 gene with fat deposition and carcass traits. Four single nuclear polymorphisms were identified, including g.161969 T>C, g.161962 A>G, g.161953 C>G and g.161904 G>T, and subsequently genotyped in five pure breeds...
November 2016: Molecular Biology Reports
https://www.readbyqxmd.com/read/27502971/conservation-and-divergence-within-the-clathrin-interactome-of-trypanosoma-cruzi
#12
Ligia Cristina Kalb, Yohana Camila A Frederico, Cordula Boehm, Claudia Maria do Nascimento Moreira, Maurilio José Soares, Mark C Field
Trypanosomatids are parasitic protozoa with a significant burden on human health. African and American trypanosomes are causative agents of Nagana and Chagas disease respectively, and speciated about 300 million years ago. These parasites have highly distinct life cycles, pathologies, transmission strategies and surface proteomes, being dominated by the variant surface glycoprotein (African) or mucins (American) respectively. In African trypanosomes clathrin-mediated trafficking is responsible for endocytosis and post-Golgi transport, with several mechanistic aspects distinct from higher organisms...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27402844/protease-activated-receptor-4-signaling-and-trafficking-is-regulated-by-the-clathrin-adaptor-protein-complex-2-independent-of-%C3%AE-arrestins
#13
Thomas H Smith, Luisa J Coronel, Julia G Li, Michael R Dores, Marvin T Nieman, JoAnn Trejo
Protease-activated receptor-4 (PAR4) is a G protein-coupled receptor (GPCR) for thrombin and is proteolytically activated, similar to the prototypical PAR1. Due to the irreversible activation of PAR1, receptor trafficking is intimately linked to signal regulation. However, unlike PAR1, the mechanisms that control PAR4 trafficking are not known. Here, we sought to define the mechanisms that control PAR4 trafficking and signaling. In HeLa cells depleted of clathrin by siRNA, activated PAR4 failed to internalize...
August 26, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27392064/human-immunodeficiency-virus-type-2-hiv-2-gag-is-trafficked-in-an-ap-3-and-ap-5-dependent-manner
#14
Justine E Alford, Michela Marongiu, Gemma L Watkins, Emma C Anderson
Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue...
2016: PloS One
https://www.readbyqxmd.com/read/27389986/genes-regulated-by-potassium-channel-tetramerization-domain-containing-15-kctd15-in-the-developing-neural-crest
#15
Thomas C B Wong, Martha Rebbert, Chengdong Wang, Xiongfong Chen, Alison Heffer, Valeria E Zarelli, Igor B Dawid, Hui Zhao
Neural crest (NC) development is controlled precisely by a regulatory network with multiple signaling pathways and the involvement of many genes. The integration and coordination of these factors are still incompletely understood. Overexpression of Wnt3a and the BMP antagonist Chordin in animal cap cells from Xenopus blastulae induces a large number of NC specific genes. We previously suggested that Potassium Channel Tetramerization Domain containing 15 (Kctd15) regulates NC formation by affecting Wnt signaling and the activity of transcription factor AP-2...
2016: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/27385343/eps15-membrane-binding-and-bending-activity-acts-redundantly-with-fcho1-during-clathrin-mediated-endocytosis
#16
Lei Wang, Adam Johnson, Michael Hanna, Anjon Audhya
Clathrin coat assembly on membranes requires cytosolic adaptors and accessory proteins, which bridge triskeleons with the lipid bilayer and stabilize lattice architecture throughout the process of vesicle formation. In Caenorhabditis elegans, the prototypical AP-2 adaptor complex, which is activated by the accessory factor Fcho1 at the plasma membrane, is dispensable during embryogenesis, enabling us to define alternative mechanisms that facilitate clathrin-mediated endocytosis. Here we uncover a synthetic genetic interaction between C...
September 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27285981/tmprss2-erg-fusion-protein-regulates-insulin-like-growth-factor-1-receptor-igf1r-gene-expression-in-prostate-cancer-involvement-of-transcription-factor-sp1
#17
Shilhav Meisel Sharon, Yair Pozniak, Tamar Geiger, Haim Werner
Prostate cancer is a major health issue in the Western world. The most common gene rearrangement in prostate cancer is the TMPRSS2-ERG fusion, which results in aberrant expression of the transcription factor ERG. The insulin-like growth factor-1 receptor (IGF1R) plays a key role in cell growth and tumorigenesis, and is overexpressed in most malignancies, including prostate cancer. In this study we show that TMPRSS2-ERG mediates its tumorigenic effects through regulation of IGF1R gene expression. Silencing of T-ERG in VCaP cells resulted in downregulation of both IGF1R and Sp1, a critical IGF1R regulator...
June 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27271794/mitochondrial-uncouplers-inhibit-clathrin-mediated-endocytosis-largely-through-cytoplasmic-acidification
#18
Wim Dejonghe, Sabine Kuenen, Evelien Mylle, Mina Vasileva, Olivier Keech, Corrado Viotti, Jef Swerts, Matyáš Fendrych, Fausto Andres Ortiz-Morea, Kiril Mishev, Simon Delang, Stefan Scholl, Xavier Zarza, Mareike Heilmann, Jiorgos Kourelis, Jaroslaw Kasprowicz, Le Son Long Nguyen, Andrzej Drozdzecki, Isabelle Van Houtte, Anna-Mária Szatmári, Mateusz Majda, Gary Baisa, Sebastian York Bednarek, Stéphanie Robert, Dominique Audenaert, Christa Testerink, Teun Munnik, Daniël Van Damme, Ingo Heilmann, Karin Schumacher, Johan Winne, Jiří Friml, Patrik Verstreken, Eugenia Russinova
ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification...
2016: Nature Communications
https://www.readbyqxmd.com/read/27270034/depfth-perception-in-clathrin-mediated-endocytosis
#19
Derek C Prosser, Beverly Wendland
The earliest stages of clathrin-coated structure (CCS) assembly involve the recruitment and stabilization of clathrin-binding adaptor proteins and the clathrin coat. In this issue of Developmental Cell, Ma et al. (2016) now identify transient protein interactions that form the basis of AP-2 adaptor complex stabilization, key to initiating CCS formation.
June 6, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27257628/activity-regulated-cytoskeleton-associated-protein-controls-ampar-endocytosis-through-a-direct-interaction-with-clathrin-adaptor-protein-2
#20
Luis L P DaSilva, Mark J Wall, Luciana P de Almeida, Sandrine C Wauters, Yunan C Januário, Jürgen Müller, Sonia A L Corrêa
The activity-regulated cytoskeleton-associated (Arc) protein controls synaptic strength by facilitating AMPA receptor (AMPAR) endocytosis. Here we demonstrate that Arc targets AMPAR to be internalized through a direct interaction with the clathrin-adaptor protein 2 (AP-2). We show that Arc overexpression in dissociated hippocampal neurons obtained from C57BL/6 mouse reduces the density of AMPAR GluA1 subunits at the cell surface and reduces the amplitude and rectification of AMPAR-mediated miniature-EPSCs (mEPSCs)...
May 2016: ENeuro
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