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https://www.readbyqxmd.com/read/28231489/moving-and-positioning-the-endolysosomal-system
#1
REVIEW
Juan S Bonifacino, Jacques Neefjes
The endolysosomal system is extremely dynamic, yet highly organized. The spatio-temporal distribution of endolysosomal organelles depends on transport driven by microtubule motors such as kinesins and dynein, and by actin-based myosin motors. It has recently become appreciated that interactions with motors are controlled by contacts with other organelles, particularly the endoplasmic reticulum (ER). The ER also controls the concentration of endolysosomal organelles in the perinuclear area, as well as their fission and fusion, through a complex system of tethering proteins...
February 20, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28231467/synaptic-vesicle-endocytosis-occurs-on-multiple-timescales-and-is-mediated-by-formin-dependent-actin-assembly
#2
Tolga Soykan, Natalie Kaempf, Takeshi Sakaba, Dennis Vollweiter, Felix Goerdeler, Dmytro Puchkov, Natalia L Kononenko, Volker Haucke
Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Recent data suggest that at physiological temperature SVs are internalized via clathrin-independent ultrafast endocytosis (UFE) within hundreds of milliseconds, while other studies have postulated a key role for clathrin-mediated endocytosis (CME) of SV proteins on a timescale of seconds to tens of seconds. Here we demonstrate using cultured hippocampal neurons as a model that at physiological temperature SV endocytosis occurs on several timescales from less than a second to several seconds, yet, is largely independent of clathrin...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28231055/the-role-of-extracellular-vesicle-micrornas-in-cancer-biology
#3
Ryou-U Takahashi, Marta Prieto-Vila, Ai Hironaka, Takahiro Ochiya
MicroRNAs (miRNAs) constitute a large family of small, approximately 20-22 nucleotide non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Multiple studies report that miRNAs are involved in homeostatic maintenance and that aberrant expression of miRNAs is often observed in various types of diseases, including cancer. In cancer biology, miRNAs exert functional roles in tumor initiation, drug resistance, and metastasis. MiRNAs are also secreted through small vesicles called exosomes, which are endosome-derived vesicles derived from various cell types including immune and tumor cells...
February 23, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28230321/disruption-of-genes-involved-in-corvet-complex-leads-to-enhanced-secretion-of-heterologous-carboxylesterase-only-in-protease-deficient-pichia-pastoris
#4
Lukas Marsalek, Clemens Gruber, Friedrich Altmann, Markus Aleschko, Diethard Mattanovich, Brigitte Gasser, Verena Puxbaum
The methylotrophic yeast Pichia pastoris (Komagataella spp.) is a popular microbial host for the production of recombinant proteins. Previous studies have shown that mis-sorting to the vacuole can be a bottleneck during production of recombinant secretory proteins in yeast, however, no information was available for P. pastoris. In this work we have therefore generated vps (vacuolar protein sorting) mutant strains disrupted in genes involved in the CORVET tethering complex at the early stages of endosomal sorting...
February 23, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28228013/highly-efficient-and-safe-delivery-of-vegf-sirna-by-bio-reducible-fluorinated-peptide-dendrimers-for-cancer-therapy
#5
Xiaojun Cai, Haofang Zhu, Yanmei Zhang, Zhongwei Gu
RNA interference (RNAi) hold great promise in treating a wide range of diseases. However, it remains highly desirable to develop new delivery systems to circumvent complex extra- and intracellular barriers for successful clinical translation. Here, we report on a versatile polymeric vector, bio-reducible fluorinated peptide dendrimers (BFPD), for highly efficient and safe delivery of siRNA. In virtue of skillfully integrated all of the unique features of reversible cross-linking, fluorination and peptide dendrimers, this novel vector can surmount almost all extra- and intracellular barriers associated with local siRNA delivery through highly improved physiological stability and serum resistance, significantly increased intratumoral enrichment, cellular uptake, as well as successful facilitation of endosomal escape and cytosolic siRNA release...
February 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28226239/structural-basis-for-the-hijacking-of-endosomal-sorting-nexin-proteins-by-chlamydia-trachomatis
#6
Blessy Paul, Hyun Sung Kim, Markus C Kerr, Wilhelmina M Huston, Rohan D Teasdale, Brett M Collins
During infection chlamydial pathogens form an intracellular membrane-bound replicative niche termed the inclusion, which is enriched with bacterial transmembrane proteins called Incs. Incs bind and manipulate host cell proteins to promote inclusion expansion and provide camouflage against innate immune responses. Sorting nexin (SNX) proteins that normally function in endosomal membrane trafficking are a major class of inclusion-associated host proteins, and are recruited by IncE/CT116. Crystal structures of the SNX5 phox-homology (PX) domain in complex with IncE define the precise molecular basis for these interactions...
February 22, 2017: ELife
https://www.readbyqxmd.com/read/28225250/membrane-anchoring-comb-like-pseudopeptides-for-efficient-ph-mediated-membrane-destabilization-and-intracellular-delivery
#7
Siyuan Chen, Shiqi Wang, Michal Kopytynski, Marie Bachelet, Rongjun Chen
Endosomal release has been identified as a rate-limiting step for intracellular delivery of therapeutic agents, in particular macromolecular drugs. Herein, we report a series of synthetic pH-responsive, membrane-anchoring polymers exhibiting dramatic endosomolytic activity for efficient intracellular delivery. The comb-like pseudopeptidic polymers were synthesized by grafting different amounts of decylamine (NDA), which act as hydrophobic membrane anchors, onto the pendant carboxylic acid groups of a pseudopeptide, poly(l-lysine iso-phthalamide)...
February 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#8
Jinxie Zhang, Danfeng Chang, Yao Yang, Xudong Zhang, Wei Tao, Lijuan Jiang, Xin Liang, Hsiangi Tsai, Laiqiang Huang, Lin Mei
Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis...
February 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28224988/post-endocytic-sorting-of-plexin-d1-controls-signal-transduction-and-development-of-axonal-and-vascular-circuits
#9
Katja Burk, Erik Mire, Anaïs Bellon, Mélanie Hocine, Jeremy Guillot, Filipa Moraes, Yutaka Yoshida, Michael Simons, Sophie Chauvet, Fanny Mann
Local endocytic events involving receptors for axon guidance cues play a central role in controlling growth cone behaviour. Yet, little is known about the fate of internalized receptors, and whether the sorting events directing them to distinct endosomal pathways control guidance decisions. Here, we show that the receptor Plexin-D1 contains a sorting motif that interacts with the adaptor protein GIPC1 to facilitate transport to recycling endosomes. This sorting process promotes colocalization of Plexin-D1 with vesicular pools of active R-ras, leading to its inactivation...
February 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28223986/gtpase-of-the-immune-associated-nucleotide-protein-5-regulates-the-lysosomal-calcium-compartment-in-t-lymphocytes
#10
Daniel Serrano, Farnaz Ghobadi, Guylain Boulay, Subburaj Ilangumaran, Christine Lavoie, Sheela Ramanathan
T lymphocytes from Gimap5(lyp/lyp) rats carrying a recessive mutation in the GTPase of immune-associated protein 5 (Gimap5) gene undergo spontaneous apoptosis. Molecular mechanisms underlying this survival defect are not yet clear. We have shown that Gimap5(lyp/lyp) T lymphocytes display reduced calcium influx following T cell antigen receptor (TCR) stimulation that was associated with impaired buffering of calcium by mitochondria. Here, we investigated the subcellular localization of GIMAP5 and its influence on Ca(2+) response in HEK293T cells and T lymphocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223800/comparison-of-the-cellular-transport-mechanism-of-cationic-star-shaped-polymers-and-liposomes-in-hacat-cells
#11
Heng-Cong Luo, Na Li, Li Yan, Kai-Jin Mai, Kan Sun, Wei Wang, Guo-Juan Lao, Chuan Yang, Li-Ming Zhang, Meng Ren
Several biological barriers must be overcome to achieve efficient nonviral gene delivery. These barriers include target cell uptake, lysosomal degradation, and dissociation from the carrier. In this study, we compared the differences in the uptake mechanism of cationic, star-shaped polymer/MMP-9siRNA complexes (β-CD-(D3)7/MMP-9siRNA complexes: polyplexes) and commercial liposome/MMP-9siRNA complexes (Lipofectamine(®) 2000/MMP-9siRNA complexes: liposomes). The uptake pathway and transfection efficiency of the polyplexes and liposomes were determined by fluorescence microscopy, flow cytometry, and reverse transcriptase-polymerase chain reaction...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28223337/functional-expression-of-dopamine-d2-receptor-is-regulated-by-tetraspanin-7-mediated-postendocytic-trafficking
#12
Seol-Ae Lee, Yeongjun Suh, Saebom Lee, Jaehoon Jeong, Soo Jeong Kim, So Jung Kim, Sang Ki Park
The dopaminergic system plays an essential role in various functions of the brain, including locomotion, memory, and reward, and the deregulation of dopaminergic signaling as a result of altered functionality of dopamine D2 receptor (DRD2) is implicated in multiple neurologic and psychiatric disorders. Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Here, we tested the hypothesis that TSPAN7 may be a binding partner of DRD2 that is involved in the regulation of its functional activity...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28222213/rab7a-regulates-tau-secretion
#13
Lilia Rodriguez, Nguyen-Vi Mohamed, Alexandre Desjardins, Roger Lippé, Edward Fon, Nicole Leclerc
The axonal microtubule-associated protein TAU, involved in Alzheimer's disease (AD), can be found in the extracellular space where it could be taken up by neurons, an event that is believed to contribute to the propagation of tau pathology in the brain. Since the small GTPase Rab7A is involved in the trafficking of endosomes, autophagosomes and lysosomes, and RAB7A gene expression and protein levels are upregulated in AD patients, we tested the hypothesis that Rab7A was involved in Tau secretion. We previously reported that both primary cortical neurons and HeLa cells overexpressing human TAU can release Tau...
February 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28220414/quantitative-analysis-of-ligand-induced-endocytosis-of-flagellin-sensing-2-using-automated-image-segmentation
#14
Michelle E Leslie, Antje Heese
Plants are equipped with a suite of plant pattern recognition receptors (PRRs) that must be properly trafficked to and from the plasma membrane (PM), which serves as the host-pathogen interface, for robust detection of invading pathogenic microbes. Recognition of bacterial flagellin, or the derived peptide flg22, is facilitated by the PM-localized PRR, FLAGELLIN SENSING 2 (FLS2). Upon flg22 binding, FLS2 is rapidly internalized from the PM into endosomal compartments and subsequently degraded. To understand better the integration of FLS2 endocytosis and signaling outputs, we developed methods for the quantitative analysis of FLS2 trafficking using freely available bioimage informatic tools...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28218918/transgenic-expression-of-human-apol1-risk-variants-in-podocytes-induces-kidney-disease-in-mice
#15
Pazit Beckerman, Jing Bi-Karchin, Ae Seo Deok Park, Chengxiang Qiu, Patrick D Dummer, Irfana Soomro, Carine M Boustany-Kari, Steven S Pullen, Jeffrey H Miner, Chien-An A Hu, Tibor Rohacs, Kazunori Inoue, Shuta Ishibe, Moin A Saleem, Matthew B Palmer, Ana Maria Cuervo, Jeffrey B Kopp, Katalin Susztak
African Americans have a heightened risk of developing chronic and end-stage kidney disease, an association that is largely attributed to two common genetic variants, termed G1 and G2, in the APOL1 gene. Direct evidence demonstrating that these APOL1 risk alleles are pathogenic is still lacking because the APOL1 gene is present in only some primates and humans; thus it has been challenging to demonstrate experimental proof of causality of these risk alleles for renal disease. Here we generated mice with podocyte-specific inducible expression of the APOL1 reference allele (termed G0) or each of the risk-conferring alleles (G1 or G2)...
February 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28216176/glutathione-reduces-cytotoxicity-of-polyethyleneimine-coated-magnetic-nanoparticles-in-cho-cells
#16
Klemen Strojan, Jasna Lojk, Vladimir B Bregar, Peter Veranič, Mojca Pavlin
Polyethyleneimine (PEI) is a polycationic compound frequently used as a transfection agent. However, cytotoxicity of PEI and PEI-coated nanoparticles (PEI NPs) is still a major obstacle in its use. In this study we report a method for reducing cytotoxicity of PEI NPs by addition of glutathione in NPs synthesis. Glutathione reduced cytotoxic effects for at least 30% and decreased observed oxidative stress response compared to standard formulation. Results showed that the effect was partially due to reduced zeta potential and partially due to protective antioxidant properties of glutathione...
February 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28216144/patient-ipsc-derived-neurons-for-disease-modeling-of-frontotemporal-dementia-with-mutation-in-chmp2b
#17
Yu Zhang, Benjamin Schmid, Nanett K Nikolaisen, Mikkel A Rasmussen, Blanca I Aldana, Mikkel Agger, Kirstine Calloe, Tina C Stummann, Hjalte M Larsen, Troels T Nielsen, Jinrong Huang, Fengping Xu, Xin Liu, Lars Bolund, Morten Meyer, Lasse K Bak, Helle S Waagepetersen, Yonglun Luo, Jørgen E Nielsen, Bjørn Holst, Christian Clausen, Poul Hyttel, Kristine K Freude
The truncated mutant form of the charged multivesicular body protein 2B (CHMP2B) is causative for frontotemporal dementia linked to chromosome 3 (FTD3). CHMP2B is a constituent of the endosomal sorting complex required for transport (ESCRT) and, when mutated, disrupts endosome-to-lysosome trafficking and substrate degradation. To understand the underlying molecular pathology, FTD3 patient induced pluripotent stem cells (iPSCs) were differentiated into forebrain-type cortical neurons. FTD3 neurons exhibited abnormal endosomes, as previously shown in patients...
February 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28215617/genetic-engineering-alveolar-macrophages-for-host-resistance-to-prrsv
#18
REVIEW
Randall S Prather, Kristin M Whitworth, Susan K Schommer, Kevin D Wells
Standard strategies for control of porcine reproductive and respiratory syndrome virus (PRRSV) have not been effective, as vaccines have not reduced the prevalence of disease and many producers depopulate after an outbreak. Another method of control would be to prevent the virus from infecting the pig. The virus was thought to infect alveolar macrophages by interaction with a variety of cell surface molecules. One popular model had PRRSV first interacting with heparin sulfate followed by binding to sialoadhesin and then being internalized into an endosome...
February 10, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28215292/emergent-role-of-coronin-1a-in-neuronal-signaling
#19
M Martorella, K Barford, B Winkler, C D Deppmann
The Coronin family of proteins were first noted for their role in pathogen-host interactions and for modulating actin dynamics. Recently, however, Coronins have been found in a greater variety of cell types, and novel roles for the Coronins within the nervous system have been discovered. In the immune system, Coronin-1a enables Mycobacterium tuberculosis to evade lysosomal destruction. This activity appears to be analogous to protection of the NGF-TrkA signaling endosome during sympathetic nervous system development that is required for survival signaling...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28214610/virosome-bound-antigen-enhances-dc-dependent-specific-cd4-t-cell-stimulation-inducing-a-th1-and-treg-profile-in-vitro
#20
Rebecca A M Blom, Mario Amacker, Christian Moser, R Maarten van Dijk, Raffaela Bonetti, Emilie Seydoux, Sean R R Hall, Christophe von Garnier, Fabian Blank
There is considerable interest to develop antigen-carriers for immune-modulatory clinical applications, but insufficient information is available on their effects on antigen-presenting cells. We employed virosomes coupled to ovalbumin (OVA) to study their interaction with murine bone marrow-derived dendritic cells (BMDCs) and modulation of downstream T cell responses. BMDCs were treated in vitro with virosomes or liposomes prior to determining BMDC phenotype, viability, and intra-cellular trafficking. Antigen-specific CD4(+) T cell activation was measured by co-culture of BMDCs with DO11...
February 15, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
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