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https://www.readbyqxmd.com/read/28326772/illuminating-the-reaction-pathways-of-viromimetic-assembly
#1
Hande E Cingil, Emre B Boz, Giovanni Biondaro, Renko de Vries, Martien A Cohen Stuart, Daniela J Kraft, Paul van der Schoot, Joris Sprakel
The co-assembly of well-defined biological nanostructures relies on a delicate balance between attractive and repulsive interactions between biomolecular building blocks. Viral capsids are a prototypical example, where coat proteins exhibit not only self-interactions but also interact with the cargo they encapsulate. In Nature the balance between antagonistic and synergistic interactions is evolved to avoid kinetic trapping and polymorphism. To date it has remained a major challenge to experimentally disentangle the complex kinetic reaction pathways that underlie successful co-assembly of biomolecular building blocks in a non-invasive approach with high temporal resolution...
March 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28325042/enhanced-endosomal-escape-by-light-fueled-liquid-metal-transformer
#2
Yue Lu, Yiliang Lin, Zhaowei Chen, Quanyin Hu, Yang Liu, Shuangjiang Yu, Wei Gao, Michael D Dickey, Zhen Gu
Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of the endosomal escape strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by the systemic toxicity and lack of specificity. We describe here a light-fueled liquid-metal transformer for effective endosomal escape-facilitated cargo delivery via a chemical-mechanical process. The nanoscale transformer can be prepared by a simple approach of sonicating a low-toxicity liquid-metal...
March 22, 2017: Nano Letters
https://www.readbyqxmd.com/read/28323110/yeast-mediated-mrna-delivery-polarizes-immuno-suppressive-macrophages-towards-an-immuno-stimulatory-phenotype
#3
Michelle Seif, Jessica Hoppstädter, Frank Breinig, Alexandra K Kiemer
Macrophages have increasingly gained interest as a therapeutic target since they represent an integral component of the tumor microenvironment. In fact, M2 macrophage accumulation in solid tumors is associated with poor prognosis and therapy failure. Therefore, reprogramming M2 macrophages towards an M1 phenotype with anti-tumor activity by gene therapy represents a promising therapeutic approach. Herein, we describe recombinant Saccharomyces cerevisiae as a novel gene delivery vehicle for primary human macrophages...
March 17, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28317069/deciphering-the-role-of-ectosomes-in-cancer-development-and-progression-focus-on-the-proteome
#4
REVIEW
Magdalena Surman, Ewa Stępień, Dorota Hoja-Łukowicz, Małgorzata Przybyło
Ectosomes are small heterogeneous membrane vesicles generated by budding from the plasma membrane in a variety of cell types and, more frequently, in tumor cells. They are shed into the extracellular space and are proposed as a novel form of intracellular communication in which information is transmitted from the originating cell to recipient cells without direct cell-to-cell contact. This review focuses on a single population of extracellular vesicles-ectosomes. We summarize recent studies of tumor-derived ectosomes which examine their biogenesis and protein cargo, and their influence on different aspects of cancer progression...
March 19, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28315083/achieving-the-promise-of-therapeutic-extracellular-vesicles-the-devil-is-in-details-of-therapeutic-loading
#5
REVIEW
Dhruvitkumar S Sutaria, Mohamed Badawi, Mitch A Phelps, Thomas D Schmittgen
Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells...
March 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28302911/real-time-insights-into-regulated-exocytosis
#6
REVIEW
Duy T Tran, Kelly G Ten Hagen
Real-time imaging of regulated exocytosis in secreting organs can provide unprecedented temporal and spatial detail. Here, we highlight recent advances in 3D time-lapse imaging in Drosophila salivary glands at single-granule resolution. Using fluorescently labeled proteins expressed in the fly, it is now possible to image the dynamics of vesicle biogenesis and the cytoskeletal factors involved in secretion. 3D imaging over time allows one to visualize and define the temporal sequence of events, including clearance of cortical actin, fusion pore formation, mixing of the vesicular and plasma membranes and recruitment of components of the cytoskeleton...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28300630/functionalized-single-walled-carbon-nanotubes-cellular-uptake-biodistribution-and-applications-in-drug-delivery
#7
Zixian Li, Andre Luis Branco de Barros, Daniel Cristian Ferreira Soares, Sara Nicole Moss, Laleh Alisaraie
The unique properties of single-walled carbon nanotubes (SWNTs) enable them to play important roles in many fields. One of their functional roles is to transport cargo into the cell. SWNTs are able to traverse amphipathic cell membranes due to their large surface area, flexible interactions with cargo, customizable dimensions, and surface chemistry. The cargoes delivered by SWNTs include peptides, proteins, nucleic acids, as well as drug molecules for therapeutic purpose. The drug delivery functions of SWNTs have been explored over the past decade...
March 11, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28299521/dynamic-of-contribution-of-ubpy-sorted-cargo-to-acrosome-biogenesis-effects-of-its-derailment-in-a-mouse-model-of-globozoospermia-the-infertile-vps54-l967q-mutant
#8
Mariarosa Gioria, Maria Enrica Pasini, Giovanna Berruti
The sperm acrosome is a specialized vacuole, a member of the family of cell-specific lysosome-related organelles. Its exocytosis, the acrosome reaction, is a crucial event during fertilization. The released acrosomal contents promote sperm penetration through the investments of the oocyte, whereas the membranous components of the acrosome are involved in sperm-oocyte interaction/fusion and oocyte activation. The way that these functionally distinct acrosomal costituents reach the vacuole during its biogenesis remains poorly understood...
March 15, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28298493/deubiquitinating-enzymes-ubp2-and-ubp15-regulate-endocytosis-by-limiting-ubiquitination-and-degradation-of-arts
#9
Hsuan-Chung Ho, Jason A MacGurn, Scott D Emr
Endocytic downregulation of cell-surface proteins is a fundamental cellular process for cell survival and adaptation to environmental stimuli. Ubiquitination of cargo proteins serves as the sorting signal for downstream trafficking, and relies on the Rsp5-ART (arrestin-related trafficking adaptors) ubiquitin ligase adaptor network in yeast. Hence, proper regulation of the abundance and activity of these ligase-adaptor complexes is critical for maintenance of optimal plasma membrane (PM) protein composition...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28298486/protein-arginine-methyltransferases-interact-with-ift-particles-and-change-location-during-flagellar-growth-and-resorption
#10
Katsutoshi Mizuno, Roger D Sloboda
Changes in protein activity driven by post translational modifications comprise an important mechanism for the control of many cellular processes. Several flagellar proteins are methylated on arginine residues during flagellar resorption; however, the function is not understood. To learn more about the role of protein methylation during flagellar dynamics, we have focused on protein arginine methyltransferases (PRMTs) 1, 3, 5, and 10. These PRMTs localize to the tip of flagella and in a punctate pattern along the length, very similar, but not identical, to that of intraflagellar transport (IFT) components...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28296562/immunomodulatory-yersinia-outer-proteins-yops-useful-tools-for-bacteria-and-humans-alike
#11
Benjamin Grabowski, M Alexander Schmidt, Christian Rüter
Human-pathogenic Yersinia produce plasmid-encoded Yersinia outer proteins (Yops), which are necessary to down-regulate anti-bacterial responses that constrict bacterial survival in the host. These Yops are effectively translocated directly from the bacterial into the target cell cytosol by the type III secretion system (T3SS). Cell-penetrating peptides (CPPs) in contrast are characterized by their ability to autonomously cross cell membranes and to transport cargo - independent of additional translocation systems...
March 15, 2017: Virulence
https://www.readbyqxmd.com/read/28294160/immune-complexes-in-chronic-chagas-disease-patients-are-formed-by-exovesicles-from-trypanosoma-cruzi-carrying-the-conserved-masp-n-terminal-region
#12
Isabel María Díaz Lozano, Luis Miguel De Pablos, Silvia Andrea Longhi, María Paola Zago, Alejandro Gabriel Schijman, Antonio Osuna
The exovesicles (EVs) are involved in pathologic host-parasite immune associations and have been recently used as biomarkers for diagnosis of infectious diseases. The release of EVs by Trypanosoma cruzi, the causative agent of Chagas disease, has recently been described, with different protein cargoes including the MASP multigene family of proteins MASPs are specific to this parasite and characterized by a conserved C-terminal (C-term) region and an N-terminal codifying for a signal peptide (SP). In this investigation, we identified immature MASP proteins containing the MASP SP in EVs secreted by the infective forms of the parasite...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28294115/phosphorylation-of-rab-coupling-protein-by-lmtk3-controls-rab14-dependent-epha2-trafficking-to-promote-cell-cell-repulsion
#13
Christine Gundry, Sergi Marco, Elena Rainero, Bryan Miller, Emmanuel Dornier, Louise Mitchell, Patrick T Caswell, Andrew D Campbell, Anna Hogeweg, Owen J Sansom, Jennifer P Morton, Jim C Norman
The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis in vivo is unclear. Here we identify an RTK of the Eph family, EphA2, to be a cargo of an RCP-regulated endocytic pathway which controls cell:cell repulsion and metastasis in vivo. Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart...
March 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28291807/the-meckel-syndrome-associated-protein-mks1-functionally-interacts-with-components-of-the-bbsome-and-ift-complexes-to-mediate-ciliary-trafficking-and-hedgehog-signaling
#14
Sarah C Goetz, Fiona Bangs, Chloe L Barrington, Nicholas Katsanis, Kathryn V Anderson
The importance of primary cilia in human health is underscored by the link between ciliary dysfunction and a group of primarily recessive genetic disorders with overlapping clinical features, now known as ciliopathies. Many of the proteins encoded by ciliopathy-associated genes are components of a handful of multi-protein complexes important for the transport of cargo to the basal body and/or into the cilium. A key question is whether different complexes cooperate in cilia formation, and whether they participate in cilium assembly in conjunction with intraflagellar transport (IFT) proteins...
2017: PloS One
https://www.readbyqxmd.com/read/28289371/exosomes-origins-and-therapeutic-potential-for-neurodegenerative-disease
#15
REVIEW
Diana K Sarko, Cindy E McKinney
Exosomes, small lipid bilayer vesicles, are part of the transportable cell secretome that can be taken up by nearby recipient cells or can travel through the bloodstream to cells in distant organs. Selected cellular cytoplasm containing proteins, RNAs, and other macromolecules is packaged into secreted exosomes. This cargo has the potential to affect cellular function in either healthy or pathological ways. Exosomal content has been increasingly shown to assist in promoting pathways of neurodegeneration such as β-amyloid peptide (Aβ) accumulation forming amyloid plaques in the brains of patients with Alzheimer's disease, and pathological aggregates of proteins containing α-synuclein in Parkinson's disease transferred to the central nervous system via exosomes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28288760/isolation-and-characterization-of-exosomes-derived-from-fertile-sheep-hydatid-cysts
#16
Mar Siles-Lucas, Carlos Sánchez-Ovejero, María González-Sánchez, Esperanza González, Juan Manuel Falcón-Pérez, Belgees Boufana, Federica Fratini, Adriano Casulli, Raúl Manzano-Román
Cystic echinococcosis (CE) is a chronic and complex zoonotic disease. Information on the mechanisms involved in parasite establishment, growth and persistence remain limited. These may be modulated by a crosstalk between extracellular vesicles (EVs). EVs including exosomes and microvesicles are able to carry developmental signaling proteins which coordinate growth and establishment of several parasites. Here, an exosome enriched EV fraction was isolated from hydatid fluid (HF) of fertile sheep cysts. A proteomic analysis of this fraction identified a number of parasite-derived vesicle-membrane associated proteins as well as cytosolic proteins...
March 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/28288128/%C3%AE-synuclein-promotes-dilation-of-the-exocytotic-fusion-pore
#17
Todd Logan, Jacob Bendor, Chantal Toupin, Kurt Thorn, Robert H Edwards
The protein α-synuclein has a central role in the pathogenesis of Parkinson's disease. Like that of other proteins that accumulate in neurodegenerative disease, however, the function of α-synuclein remains unknown. Localization to the nerve terminal suggests a role in neurotransmitter release, and overexpression inhibits regulated exocytosis, but previous work has failed to identify a clear physiological defect in mice lacking all three synuclein isoforms. Using adrenal chromaffin cells and neurons, we now find that both overexpressed and endogenous synuclein accelerate the kinetics of individual exocytotic events, promoting cargo discharge and reducing pore closure ('kiss-and-run')...
March 13, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28287860/autophagosome-formation-where-the-secretory-and-autophagy-pathways-meet
#18
Juan Wang, Saralin Davis, Ming Zhu, Elizabeth A Miller, Susan Ferro-Novick
The upregulation of autophagosome formation in response to nutrient deprivation requires significant intracellular membrane rearrangements that are poorly understood. Recent findings have implicated COPII-coated vesicles, well known as ER-Golgi cargo transport carriers, as key players in macroautophagy. The role of COPII vesicles in macroautophagy and how they interact with autophagy-related (Atg) proteins was unknown. In our recent report, we show that during nutrient deprivation, phosphorylation of the membrane-distal surface of the COPII coat subunit Sec24 facilitates the interaction of Sec24 with the Atg machinery (specifically, Atg9) to regulate the abundance of autophagosomes during starvation...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28287548/legionella-pneumophila-outer-membrane-vesicles-isolation-and-analysis-of-their-pro-inflammatory-potential-on-macrophages
#19
Anna Lena Jung, Kerstin Hoffmann, Christina E Herkt, Christine Schulz, Wilhelm Bertrams, Bernd Schmeck
Bacteria are able to secrete a variety of molecules via various secretory systems. Besides the secretion of molecules into the extracellular space or directly into another cell, Gram-negative bacteria can also form outer membrane vesicles (OMVs). These membrane vesicles can deliver their cargo over long distances, and the cargo is protected from degradation by proteases and nucleases. Legionella pneumophila (L. pneumophila) is an intracellular, Gram-negative pathogen that causes a severe form of pneumonia. In humans, it infects alveolar macrophages, where it blocks lysosomal degradation and forms a specialized replication vacuole...
February 22, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28287156/single-molecule-investigation-of-kinesin-1-motility-using-engineered-microtubule-defects
#20
Michael W Gramlich, Leslie Conway, Winnie H Liang, Joelle A Labastide, Stephen J King, Jing Xu, Jennifer L Ross
The structure of the microtubule is tightly regulated in cells via a number of microtubule associated proteins and enzymes. Microtubules accumulate structural defects during polymerization, and defect size can further increase under mechanical stresses. Intriguingly, microtubule defects have been shown to be targeted for removal via severing enzymes or self-repair. The cell's control in defect removal suggests that defects can impact microtubule-based processes, including molecular motor-based intracellular transport...
March 13, 2017: Scientific Reports
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