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https://www.readbyqxmd.com/read/29133341/the-trafficking-protein-ehd2-positively-regulates-cardiac-sarcolemmal-katp-channel-surface-expression-role-in-cardioprotection
#1
Hua Qian Yang, Kundan Jana, Michael J Rindler, William A Coetzee
ATP-sensitive K(+) (KATP) channels uniquely link cellular energy metabolism to membrane excitability and are expressed in diverse cell types that range from the endocrine pancreas to neurons and smooth, skeletal, and cardiac muscle. A decrease in the surface expression of KATP channels has been linked to various disorders, including dysregulated insulin secretion, abnormal blood pressure, and impaired resistance to cardiac injury. In contrast, up-regulation of KATP channel surface expression may be protective, for example, by mediating the beneficial effect of ischemic preconditioning...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28972287/eps15r-and-clathrin-regulate-ephb2-mediated-cell-repulsion
#2
Emma Evergren, Neville Cobbe, Harvey T McMahon
Expression of Eph receptors and their ligands, the ephrins, have important functions in boundary formation and morphogenesis in both adult and embryonic tissue. The EphB receptors and ephrinB ligands are transmembrane proteins that are expressed in different cells and their interaction drives cell repulsion. For cell repulsion to occur, trans-endocytosis of the inter-cellular receptor-ligand EphB-ephrinB complex is required. The molecular mechanism underlying trans-endocytosis is poorly defined. Here we show that the process is clathrin- and Eps15R-mediated using Co115 colorectal cell lines stably expressing EphB2 and ephrinB1...
October 3, 2017: Traffic
https://www.readbyqxmd.com/read/28956766/porcine-hemagglutinating-encephalomyelitis-virus-enters-neuro-2a-cells-via-clathrin-mediated-endocytosis-in-a-rab5-cholesterol-and-ph-dependent-manner
#3
Zi Li, Kui Zhao, Yungang Lan, Xiaoling Lv, Shiyu Hu, Jiyu Guan, Huijun Lu, Jing Zhang, Junchao Shi, Yawen Yang, Deguang Song, Feng Gao, Wenqi He
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that invades the central nervous system (CNS) in piglets. Although important progress has been made toward understanding the biology of PHEV, many aspects of its life cycle remain obscure. Here we dissected the molecular mechanism underlying cellular entry and intracellular trafficking of PHEV in mouse neuroblastoma (Neuro-2a) cells. We first performed a thin-section transmission electron microscopy (TEM) assay to characterize the kinetics of PHEV, and we found that viral entry and transfer occur via membranous coating-mediated endo- and exocytosis...
December 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28947773/anti-enterovirus-71-activities-of-melissa-officinalis-extract-and-its-biologically-active-constituent-rosmarinic-acid
#4
Sin-Guang Chen, Yann-Lii Leu, Mei-Ling Cheng, Siew Chin Ting, Ching-Chuan Liu, Shulhn-Der Wang, Cheng-Hung Yang, Cheng-Yu Hung, Hiroaki Sakurai, Kuan-Hsing Chen, Hung-Yao Ho
Enterovirus 71 (EV71) infection is endemic in the Asia-Pacific region. No specific antiviral drug has been available to treat EV71 infection. Melissa officinalis (MO) is a medicinal plant with long history of usage in the European and Middle East. We investigated whether an aqueous solution of concentrated methanolic extract (MOM) possesses antiviral activity. MOM inhibited plaque formation, cytopathic effect, and viral protein synthesis in EV71-infected cells. Using spectral techniques, we identified rosmarinic acid (RA) as a biologically active constituent of MOM...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28943089/ehd-proteins-cooperate-to-generate-caveolar-clusters-and-to-maintain-caveolae-during-repeated-mechanical-stress
#5
Ivana Yeow, Gillian Howard, Jessica Chadwick, Carolina Mendoza-Topaz, Carsten G Hansen, Benjamin J Nichols, Elena Shvets
Caveolae introduce flask-shaped convolutions into the plasma membrane and help to protect the plasma membrane from damage under stretch forces. The protein components that form the bulb of caveolae are increasingly well characterized, but less is known about the contribution of proteins that localize to the constricted neck. Here we make extensive use of multiple CRISPR/Cas9-generated gene knockout and knockin cell lines to investigate the role of Eps15 Homology Domain (EHD) proteins at the neck of caveolae...
October 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28874464/mas1-receptor-trafficking-involves-erk1-2-activation-through-a-%C3%AE-arrestin2-dependent-pathway
#6
Flavia M Cerniello, Oscar A Carretero, Nadia A Longo Carbajosa, Bruno D Cerrato, Robson A Santos, Hernán E Grecco, Mariela M Gironacci
The MAS1 receptor (R) exerts protective effects in the brain, heart, vessels, and kidney. R trafficking plays a critical function in signal termination and propagation and in R resensitization. We examined MAS1R internalization and trafficking on agonist stimulation and the role of β-arrestin2 in the activation of ERK1/2 (extracellular signal-regulated kinase 1/2) and Akt after MAS1R stimulation. Human embryonic kidney 293T cells were transfected with the coding sequence for MAS1R-YFP (MAS1R fused to yellow fluorescent protein)...
November 2017: Hypertension
https://www.readbyqxmd.com/read/28428548/antiviral-activities-of-schizonepeta-tenuifolia-briq-against-enterovirus-71-in-vitro-and-in-vivo
#7
Sin-Guang Chen, Mei-Ling Cheng, Kuan-Hsing Chen, Jim-Tong Horng, Ching-Chuan Liu, Shih-Min Wang, Hiroaki Sakurai, Yann-Lii Leu, Shulhn-Der Wang, Hung-Yao Ho
No effective drug is currently available for treatment of enterovirus 71 (EV71) infection. Schizonepeta tenuifolia Briq. (ST) has been used as a herbal constituent of traditional Chinese medicine. We studied whether the aqueous extract of Schizonepeta tenuifolia Briq (STE) has antiviral activity. STE inhibited replication of EV71, as evident by its ability to diminish plaque formation and cytopathic effect induced by EV71, and to inhibit the synthesis of viral RNA and protein. Moreover, daily single-dose STE treatment significantly improved the survival of EV71-infected mice, and ameliorated the symptoms...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28346440/endocytic-proteins-are-partitioned-at-the-edge-of-the-clathrin-lattice-in-mammalian-cells
#8
Kem A Sochacki, Andrea M Dickey, Marie-Paule Strub, Justin W Taraska
Dozens of proteins capture, polymerize and reshape the clathrin lattice during clathrin-mediated endocytosis (CME). How or if this ensemble of proteins is organized in relation to the clathrin coat is unknown. Here, we map key molecules involved in CME at the nanoscale using correlative super-resolution light and transmission electron microscopy. We localize 19 different endocytic proteins (amphiphysin1, AP2, β2-arrestin, CALM, clathrin, DAB2, dynamin2, EPS15, epsin1, epsin2, FCHO2, HIP1R, intersectin, NECAP, SNX9, stonin2, syndapin2, transferrin receptor, VAMP2) on thousands of individual clathrin structures, generating a comprehensive molecular architecture of endocytosis with nanoscale precision...
April 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28228550/interaction-of-phosphorylated-rab11-fip2-with-eps15-regulates-apical-junction-composition
#9
Lynne A Lapierre, Elizabeth H Manning, Kenya M Mitchell, Cathy M Caldwell, James R Goldenring
MARK2 regulates the establishment of polarity in Madin-Darby canine kidney (MDCK) cells in part through phosphorylation of serine 227 of Rab11-FIP2. We identified Eps15 as an interacting partner of phospho-S227-Rab11-FIP2 (pS227-FIP2). During recovery from low calcium, Eps15 localized to the lateral membrane before pS227-FIP2 arrival. Later in recovery, Eps15 and pS227-FIP2 colocalized at the lateral membrane. In MDCK cells expressing the pseudophosphorylated FIP2 mutant FIP2(S227E), during recovery from low calcium, Eps15 was trapped and never localized to the lateral membrane...
April 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28228524/structural-insights-into-the-activation-mechanism-of-dynamin-like-ehd-atpases
#10
Arthur Alves Melo, Balachandra G Hegde, Claudio Shah, Elin Larsson, J Mario Isas, Séverine Kunz, Richard Lundmark, Ralf Langen, Oliver Daumke
Eps15 (epidermal growth factor receptor pathway substrate 15)-homology domain containing proteins (EHDs) comprise a family of dynamin-related mechano-chemical ATPases involved in cellular membrane trafficking. Previous studies have revealed the structure of the EHD2 dimer, but the molecular mechanisms of membrane recruitment and assembly have remained obscure. Here, we determined the crystal structure of an amino-terminally truncated EHD4 dimer. Compared with the EHD2 structure, the helical domains are 50° rotated relative to the GTPase domain...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28215104/increased-eps15-homology-domain-1-and-rab11fip3-expression-regulate-breast-cancer-progression-via-promoting-epithelial-growth-factor-receptor-recycling
#11
Dandan Tong, Ya-Nan Liang, A A Stepanova, Yu Liu, Xiaobo Li, Letian Wang, Fengmin Zhang, N V Vasilyeva
Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28126411/perfluorooctanoic-acid-affects-endocytosis-involving-clathrin-light-chain-a-and-microrna-133b-3p-in-mouse-testes
#12
Yin Lu, Jianshe Wang, Xuejiang Guo, Shengmin Yan, Jiayin Dai
Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (>1.5-fold and P<0...
March 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28075048/the-sti-and-uba-domains-of-ubqln1-are-critical-determinants-of-substrate-interaction-and-proteostasis
#13
Zimple Kurlawala, Parag P Shah, Charmi Shah, Levi J Beverly
There are five Ubiquilin proteins (UBQLN1-4, UBQLN-L), which are evolutionarily conserved and structurally similar. UBQLN proteins have three functional domains: N-terminal ubiquitin-like domain (UBL), C-terminal ubiquitin-associated domain (UBA), and STI chaperone-like regions in the middle. Alterations in UBQLN1 gene have been detected in a variety of disorders ranging from Alzheimer's disease to cancer. UBQLN1 has been largely studied in neurodegenerative disorders in the context of protein quality control...
August 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28060904/past1-modulates-drosophila-eye-development
#14
Orly Dorot, Hermann Steller, Daniel Segal, Mia Horowitz
Endocytosis is a multi-step process involving a large number of proteins, both general factors, such as clathrin and adaptor protein complexes, and unique proteins, which modulate specialized endocytic processes, like the EHD proteins. EHDs are a family of Eps15 Homology Domain containing proteins that consists of four mammalian homologs, one C. elegans, one Drosophila melanogaster and two plants orthologs. These membrane-associated proteins are involved in different steps of endocytic trafficking pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28057762/selection-and-stabilization-of-endocytic-sites-by-ede1-a-yeast-functional-homologue-of-human-eps15
#15
Rebecca Lu, David G Drubin
During clathrin-mediated endocytosis (CME), endocytic-site maturation can be divided into two stages corresponding to the arrival of the early and late proteins at the plasma membrane. The early proteins are required to capture cargo and position the late machinery, which includes proteins involved in actin assembly and membrane scission. However, the mechanism by which early-arriving proteins select and stabilize endocytic sites is not known. Ede1, one of the earliest proteins recruited to endocytic sites, facilitates site initiation and stabilization...
March 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27811356/spatio-temporal-regulation-of-egfr-signaling-by-the-eps15-homology-domain-containing-protein-3-ehd3
#16
Mohamed Amessou, Abdul Shukkur Ebrahim, Ashok Dilly, Melvin Joseph, Marina Tabolina, Sahiti Chukkapalli, Louay Meroueh, Joseph T Syed, Allison Liddane, Siera Lanae Lang, Ayad Al-Katib, Mustapha Kandouz
The epidermal growth factor (EGF) receptor EGFR is a major receptor tyrosine kinase whose role in gliomagenesis is well established. We have recently identified EHD3 [Eps15 homology (EH) domain-containing protein 3], an endocytic trafficking regulatory protein, as a putative brain tumor suppressor. Here, we investigate the underlying mechanisms, by establishing a novel mechanistic and functional connection between EHD3 and the EGFR signaling pathway. We show that, in response to stimulation with the EGF ligand, EHD3 accelerates the rate of EGFR degradation by dramatically increasing its ubiquitination...
November 29, 2016: Oncotarget
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
#17
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...
August 15, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27611902/analysis-of-loops-that-mediate-protein-protein-interactions-and-translation-into-submicromolar-inhibitors
#18
Timothy R Siegert, Michael J Bird, Kamlesh M Makwana, Joshua A Kritzer
Effective strategies for mimicking α-helix and β-strand epitopes have been developed, producing valuable inhibitors for some classes of protein-protein interactions (PPIs). However, there are no general strategies for translating loop epitopes into useful PPI inhibitors. In this work, we use the LoopFinder program to identify diverse sets of "hot loops," which are loop epitopes that mediate PPIs. These include loops that are well-suited to mimicry with macrocyclic compounds, and loops that are most similar to variable loops on antibodies and ankyrin repeat proteins...
October 5, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27557559/epsin1-modulates-synaptic-vesicle-retrieval-capacity-at-cns-synapses
#19
Jae Won Kyung, Jae Ryul Bae, Dae-Hwan Kim, Woo Keun Song, Sung Hyun Kim
Synaptic vesicle retrieval is an essential process for continuous maintenance of neural information flow after synaptic transmission. Epsin1, originally identified as an EPS15-interacting protein, is a major component of clathrin-mediated endocytosis. However, the role of Epsin1 in synaptic vesicle endocytosis at CNS synapses remains elusive. Here, we showed significantly altered synaptic vesicle endocytosis in neurons transfected with shRNA targeting Epsin1 during/after neural activity. Endocytosis was effectively restored by introducing shRNA-insensitive Epsin1 into Epsin1-depleted neurons...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27531895/mammalian-eps15-homology-domain-1-promotes-metastasis-in-non-small-cell-lung-cancer-by-inducing-epithelial-mesenchymal-transition
#20
Qingwei Meng, Ying Xing, Tingting Ren, Hailing Lu, Yuhui Xi, Zhijun Jiang, Jing Hu, Chunhong Li, Lichun Sun, Dianjun Sun, Li Cai
The identification of the earliest molecular events responsible for the metastatic dissemination of non-small cell lung cancer (NSCLC) remains critical for early detection, prevention, and treatment interventions. In this study, we hypothesized that Mammalian Eps15 homology domain 1 (EHD1) might be responsible for the metastatic behavior of cells in NSCLC. We demonstrated that upregulation of EHD1 is associated with lymph nodes metastasis and unfavorable survival in patients with NSCLC. EHD1 knockdown inhibited the invasion and migration of human NSCLC cells, and overexpression of EHD1 increased the metastatic potential of lung cancer cells...
April 4, 2017: Oncotarget
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