keyword
MENU ▼
Read by QxMD icon Read
search

Endosomal trafficking

keyword
https://www.readbyqxmd.com/read/29150077/unique-arginine-array-improves-cytosolic-localization-of-hydrocarbon-stapled-peptides
#1
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/29146245/repurposing-cationic-amphiphilic-drugs-as-adjuvants-to-induce-lysosomal-sirna-escape-in-nanogel-transfected-cells
#2
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/29142129/entry-of-human-coronavirus-nl63-to-the-cell
#3
Aleksandra Milewska, Paulina Nowak, Katarzyna Owczarek, Artur Szczepanski, Miroslaw Zarebski, Agnieszka Hoang-Bujnowicz, Krzysztof Berniak, Jacek Wojarski, Slawomir Zeglen, Zbigniew Baster, Zenon Rajfur, Krzysztof Pyrc
First steps of human coronavirus NL63 (HCoV-NL63) infection were previously described. The virus binds to target cells by heparan sulfate proteoglycans, and interacts with the ACE2 protein. Subsequent events, including virus internalization and trafficking, remain to be elucidated. In this study, we mapped the process of HCoV-NL63 entry into LLC-Mk2 cell line and ex vivo 3D tracheobronchial tissue.Using a variety of techniques we have shown that HCoV-NL63 virions require endocytosis for successful entry to the LLC-MK2 cells, and interaction between the virus and the ACE2 molecule triggers recruitment of clathrin...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142073/gga1-regulates-signal-dependent-sorting-of-bace1-to-recycling-endosomes-which-moderates-a%C3%AE-production
#4
Wei Hong Toh, Pei Zhi Cheryl Chia, Mohammed Iqbal Hossain, Paul A Gleeson
The diversion of the membrane-bound β-secretase BACE1 from the endo-lysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the SNX4-mediated, signal independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the acidic cluster-dileucine DISLL cytoplasmic tail motif of BACE1...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29140158/endosomal-trafficking-regulates-receptor-mediated-transcytosis-of-antibodies-across-the-blood-brain-barrier
#5
Arsalan S Haqqani, Christie E Delaney, Eric Brunette, Ewa Baumann, Graham K Farrington, William Sisk, John Eldredge, Wen Ding, Tammy-Lynn Tremblay, Danica B Stanimirovic
Current methods for examining antibody trafficking are either non-quantitative such as immunocytochemistry or require antibody labeling with tracers. We have developed a multiplexed quantitative method for antibody 'tracking' in endosomal compartments of brain endothelial cells. Rat brain endothelial cells were co-incubated with blood-brain barrier (BBB)-crossing FC5, monovalent FC5Fc or bivalent FC5Fc fusion antibodies and control antibodies. Endosomes were separated using sucrose-density gradient ultracentrifugation and analyzed using multiplexed mass spectrometry to simultaneously quantify endosomal markers, receptor-mediated transcytosis (RMT) receptors and the co-incubated antibodies in each fraction...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29134778/the-axonal-endoplasmic-reticulum-one-organelle-many-functions-in-development-maintenance-and-plasticity
#6
REVIEW
Alejandro Luarte, Víctor Hugo Cornejo, Francisca Bertin, Javiera Gallardo, Andrés Couve
The endoplasmic reticulum (ER) is highly conserved in eukaryotes and neurons. Indeed, the localization of the organelle in axons has been known for nearly half a century. However, the relevance the axonal ER is only beginning to emerge. In this review we discuss the structure of the ER in axons, examining the role of ER-shaping proteins and highlighting reticulons. We analyze the multiple functions of the ER and their potential contribution to axonal physiology. First we examine the emerging roles of the axonal ER in lipid synthesis, protein translation, processing, quality control and secretory trafficking of transmembrane proteins...
November 14, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/29130884/ubiquitin-turnover-and-endocytic-trafficking-in-yeast-are-regulated-by-ser57-phosphorylation-of-ubiquitin
#7
Sora Lee, Jessica M Tumolo, Aaron C Ehlinger, Kristin K Jernigan, Susan J Qualls-Histed, Pi-Chiang Hsu, W Hayes McDonald, Walter J Chazin, Jason A MacGurn
Despite its central role in protein degradation little is known about the molecular mechanisms that sense, maintain, and regulate steady state concentration of ubiquitin in the cell. Here, we describe a novel mechanism for regulation of ubiquitin homeostasis that is mediated by phosphorylation of ubiquitin at the Ser57 position. We find that loss of Ppz phosphatase activity leads to defects in ubiquitin homeostasis that are at least partially attributable to elevated levels of Ser57 phosphorylated ubiquitin...
November 13, 2017: ELife
https://www.readbyqxmd.com/read/29130391/the-vici-syndrome-protein-epg5-regulates-intracellular-nucleic-acid-trafficking-linking-autophagy-to-innate-and-adaptive-immunity
#8
E Piano Mortari, V Folgiero, V Marcellini, P Romania, E Bellacchio, V D'Alicandro, C Bocci, R Carrozzo, D Martinelli, S Petrini, E Axiotis, C Farroni, F Locatelli, U Schara, D Pilz, H Jungbluth, C Dionisi-Vici, R Carsetti
Vici syndrome is a human inherited multi-system disorder caused by recessive mutations in EPG5, encoding the EPG5 protein that mediates the fusion of autophagosomes with lysosomes. Immunodeficiency characterized by lack of memory B cells and increased susceptibility to infection is an integral part of the condition, but the role of EPG5 in the immune system remains unknown. Here we show that EPG5 is indispensable for the transport of the TLR9 ligand CpG to the late endosomal-lysosomal compartment, and for TLR9-initiated signaling, a step essential for the survival of human memory B cells and their ultimate differentiation into plasma cells...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29118375/the-lipid-raft-dwelling-protein-us9-can-be-manipulated-to-target-app-compartmentalization-app-processing-and-neurodegenerative-disease-pathogenesis
#9
Renato Brandimarti, Gordon S Hill, Jonathan D Geiger, Olimpia Meucci
The trafficking behavior of the lipid raft-dwelling US9 protein from Herpes Simplex Virus strikingly overlaps with that of the amyloid precursor protein (APP). Both US9 and APP processing machinery rely on their ability to shuttle between endosomes and plasma membranes, as well as on their lateral accumulation in lipid rafts. Therefore, repurposing US9 to track/modify these molecular events represents a valid approach to investigate pathological states including Alzheimer's disease and HIV-associated neurocognitive disorders where APP misprocessing to amyloid beta formation has been observed...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117568/pten-regulates-glucose-transporter-recycling-by-impairing-snx27-retromer-assembly
#10
Swapnil Rohidas Shinde, Subbareddy Maddika
The tumor suppressor PTEN executes cellular functions predominantly through its phosphatase activity. Here we identified a phosphatase-independent role for PTEN during vesicular trafficking of the glucose transporter GLUT1. PTEN physically interacts with SNX27, a component of the retromer complex that recycles transmembrane receptors such as GLUT1 from endosomes to the plasma membrane. PTEN binding with SNX27 prevents GLUT1 accumulation at the plasma membrane because of defective recycling and thus reduces cellular glucose uptake...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29109534/natural-history-of-helicobacter-pylori-vaca-toxin-in-human-gastric-epithelium-in-vivo-vacuoles-and-beyond
#11
Vittorio Necchi, Patrizia Sommi, Alessandro Vanoli, Roberto Fiocca, Vittorio Ricci, Enrico Solcia
Uptake, intracellular trafficking and pathologic effects of VacA toxin from Helicobacter pylori have been widely investigated in vitro. However, no systematic analysis investigated VacA intracellular distribution and fate in H. pylori-infected human gastric epithelium in vivo, using ultrastructural immunocytochemistry that combines precise toxin localization with analysis of the overall cell ultrastructure and intercompartimental/interorganellar relationships. By immunogold procedure, in this study we investigated gastric biopsies taken from dyspeptic patients to characterize the overall toxin's journey inside human gastric epithelial cells in vivo...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29099291/post-translational-modifications-how-to-modulate-rab7-functions
#12
Graziana Modica, Stephane Lefrancois
The small GTPase Rab7 is the main regulator of membrane trafficking at late endosomes. This small GTPase regulates endosome-to-trans Golgi Network trafficking of sorting receptors, membrane fusion of late endosomes to lysosomes, and autophagosomes to lysosomes during autophagy. Rab7, like all Rab GTPases, binds downstream effectors coordinating several divergent pathways. How cells regulate these interactions and downstream functions is not well understood. Recent evidence suggests that Rab7 function can be modulated by the combination of several post-translational modifications that facilitate interactions with one effector while preventing binding to another one...
November 3, 2017: Small GTPases
https://www.readbyqxmd.com/read/29097235/unc93b1-is-essential-for-cytokine-activation-of-five-pamps-in-the-orange-spotted-grouper-epinephelus-coioides
#13
Yaosi Liang, Yu Wang, Liangge He, Jianan He, Wan Peng, Libin Zhou, Yong Zhang, Haifa Zhang, Herong Shi, Haoran Lin, Danqi Lu
Toll-like receptors (TLRs) are important innate immune receptors that recognize multiple pathogen-associated molecular patterns (PAMPs) and activate the immune responses to resist the invasion of pathogens. Many TLRs need assistance from trafficking chaperones to transport to the specific cell compartments and then are processed before they are activated. In this study, we identified an important trafficking chaperone, Unc-93 homolog B1 (unc93b1), from the Epinephelus coioides (orange-spotted grouper). The deduced protein sequence of Eco...
October 31, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29093485/dynamic-fingerprinting-of-sub-cellular-nanostructures-by-image-mean-square-displacement-analysis
#14
Luca Digiacomo, Francesca D'Autilia, William Durso, Paolo Maria Tentori, Giulio Caracciolo, Francesco Cardarelli
Here we provide demonstration that image mean square displacement (iMSD) analysis is a fast and robust platform to address living matter dynamic organization at the level of sub-cellular nanostructures (e.g. endocytic vesicles, early/late endosomes, lysosomes), with no a-priori knowledge of the system, and no need to extract single trajectories. From each iMSD, a unique triplet of average parameters (namely: diffusivity, anomalous coefficient, size) are extracted and represented in a 3D parametric space, where clustering of single-cell points readily defines the structure "dynamic fingerprint", at the whole-cell-population level...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29090275/activation-of-tpa-response-element-present-in-human-lemur-tyrosine-kinase-2-lmtk2-gene-increases-its-expression
#15
Isha Dey, Neil A Bradbury
Regulatory elements present in the promoter of a gene drive the expression of the gene in response to various stimuli. Lemur Tyrosine Kinase 2 (LMTK2) is a membrane-anchored Serine/Threonine kinase involved in endosomal protein trafficking and androgen signaling amongst other processes. Previous studies have shown this protein to be of therapeutic importance in cystic fibrosis and prostate cancer. However, nothing is known about the endogenous expression of this protein and its regulation. In this study, we analyzed the gene encoding human LMTK2, to look for possible regulatory elements that could affect its expression...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29084199/class-iii-phosphatidylinositol-3-oh-kinase-controls-epithelial-integrity-through-endosomal-lkb1-regulation
#16
Fergal O'Farrell, Viola Hélène Lobert, Marte Sneeggen, Ashish Jain, Nadja Sandra Katheder, Eva Maria Wenzel, Sebastian Wolfgang Schultz, Kia Wee Tan, Andreas Brech, Harald Stenmark, Tor Erik Rusten
The molecular mechanisms underlying the interdependence between intracellular trafficking and epithelial cell polarity are poorly understood. Here we show that inactivation of class III phosphatidylinositol-3-OH kinase (CIII-PI3K), which produces phosphatidylinositol-3-phosphate (PtdIns3P) on endosomes, disrupts epithelial organization. This is caused by dysregulation of endosomally localized Liver Kinase B1 (LKB1, also known as STK11), which shows delocalized and increased activity accompanied by dysplasia-like growth and invasive behaviour of cells provoked by JNK pathway activation...
October 30, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29084197/tbc1d23-is-a-bridging-factor-for-endosomal-vesicle-capture-by-golgins-at-the-trans-golgi
#17
John J H Shin, Alison K Gillingham, Farida Begum, Jessica Chadwick, Sean Munro
The specificity of membrane traffic involves tethers at destination organelles that selectively capture incoming transport vesicles to allow SNAREs on opposing membranes to then assemble and drive fusion. Tethers include both protein complexes and long coiled-coil proteins, although how they contribute to specificity remains unclear. The golgin coiled-coil proteins at the Golgi apparatus capture vesicles from different origins, but the vesicle-specific molecular cues that they recognize are unknown. Vesicle tethering is typically a transient process and therefore is challenging to interrogate in vivo...
October 30, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29069646/the-intracranial-aneurysm-gene-thsd1-connects-endosome-dynamics-to-nascent-focal-adhesion-assembly
#18
Yan-Ning Rui, Zhen Xu, Xiaoqian Fang, Miriam R Menezes, Julien Balzeau, Airu Niu, John P Hagan, Dong H Kim
BACKGROUND/AIMS: We recently discovered that harmful variants in THSD1 (Thrombospondin type-1 domain-containing protein 1) likely cause intracranial aneurysm and subarachnoid hemorrhage in a subset of both familial and sporadic patients with supporting evidence from two vertebrate models. The current study seeks to elucidate how THSD1 and patient-identified variants function molecularly in focal adhesions. METHODS: Co-immunostaining and co-immunoprecipitation were performed to define THSD1 subcellular localization and interacting partners...
October 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29068384/shiga-toxin-a-model-for-glycolipid-dependent-and-lectin-driven-endocytosis
#19
REVIEW
Ludger Johannes
The cellular entry of the bacterial Shiga toxin and the related verotoxins has been scrutinized in quite some detail. This is due to their importance as a threat to human health. At the same time, the study of Shiga toxin has allowed the discovery of novel molecular mechanisms that also apply to the intracellular trafficking of endogenous proteins at the plasma membrane and in the endosomal system. In this review, the individual steps that lead to Shiga toxin uptake into cells will first be presented from a purely mechanistic perspective...
October 25, 2017: Toxins
https://www.readbyqxmd.com/read/29065163/drosophila-vamp7-regulates-wingless-intracellular-trafficking
#20
Han Gao, Fang He, Xinhua Lin, Yihui Wu
Drosophila Wingless (Wg) is a morphogen that determines cell fate during development. Previous studies have shown that endocytic pathways regulate Wg trafficking and signaling. Here, we showed that loss of vamp7, a gene required for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling. Interestingly, we found that levels of Dally-like (Dlp), a glypican that can interact with Wg to suppress Wg signaling at the dorsoventral boundary of the Drosophila wing, were also increased in vamp7 mutant cells...
2017: PloS One
keyword
keyword
87950
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"