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Cargo protein

Fengyan Deng, Nancy Magee, Yuxia Zhang
Cell-to-cell communication is a fascinating process that is essential for maintaining tissue and whole-body homeostasis. Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles that are a means of communication between cells. Accumulating evidence indicates that EVs can render either beneficial or harmful outcomes, depending on the specific cargos (e.g. proteins, lipids, RNAs) transferred between cells. EVs also have great value as diagnostic and prognostic markers of disease because they are present in a variety of biological fluids and carry bioactive molecules from their cells or tissues of origin...
September 2017: Liver Research
Eugene Jennifer Jin, Ferdi Ridvan Kiral, Mehmet Neset Ozel, Lara Sophie Burchardt, Marc Osterland, Daniel Epstein, Heike Wolfenberg, Steffen Prohaska, Peter Robin Hiesinger
Neurons are highly polarized cells that require continuous turnover of membrane proteins at axon terminals to develop, function, and survive. Yet, it is still unclear whether membrane protein degradation requires transport back to the cell body or whether degradation also occurs locally at the axon terminal, where live observation of sorting and degradation has remained a challenge. Here, we report direct observation of two cargo-specific membrane protein degradation mechanisms at axon terminals based on a live-imaging approach in intact Drosophila brains...
March 3, 2018: Current Biology: CB
Chen Fu, Yonggang Xiang, Xiaorong Li, Ailing Fu
For successful theranosis of brain diseases, limited access of therapeutic molecules across blood-brain barrier (BBB) needs be overcome in brain delivery. Currently, peptide derivatives of rabies virus glycoprotein (RVG) have been exploited as delivery ligands to transport nanocarriers across BBB and specifically into the brain. The targeting peptides usually conjugate to the nanocarrier surface, and the cargoes, including siRNA, miRNA, DNA, proteins and small molecular chemicals, are complexed or encapsulated in the nanocarriers...
June 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Alice Ossoli, Chiara Pavanello, Eleonora Giorgio, Laura Calabresi, Monica Gomaraschi
Hypercholesterolemia is one of the main risk factors for the development of atherosclerosis. Among the various lipoprotein classes, however, high density lipoproteins (HDL) are inversely associated with the incidence of atherosclerosis, since they are able to exert a series of atheroprotective functions. The central role of HDL within the reverse cholesterol transport, their antioxidant and anti-inflammatory properties and their ability to preserve endothelial homeostasis are likely responsible for HDL-mediated atheroprotection...
March 15, 2018: Current Medicinal Chemistry
Cristian De Gregorio, Paula Díaz, Rodrigo López-Leal, Patricio Manque, Felipe A Court
Exosomes are small (30-150 nm) vesicles of endosomal origin secreted by most cell types. Exosomes contain proteins, lipids, and RNA species including microRNA, mRNA, rRNA, and long noncoding RNAs. The mechanisms associated with exosome synthesis and cargo loading are still poorly understood. A role for exosomes in intercellular communication has been reported in physiological and pathological conditions both in vitro and in vivo. Previous studies have suggested that Schwann cell-derived exosomes regulate neuronal functions, but the mechanisms are still unclear...
2018: Methods in Molecular Biology
Hilary C Archbold, Kasey L Jackson, Ayush Arora, Kaitlin Weskamp, Elizabeth M-H Tank, Xingli Li, Roberto Miguez, Robert D Dayton, Sharon Tamir, Ronald L Klein, Sami J Barmada
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders marked in most cases by the nuclear exclusion and cytoplasmic deposition of the RNA binding protein TDP43. We previously demonstrated that ALS-associated mutant TDP43 accumulates within the cytoplasm, and that TDP43 mislocalization predicts neurodegeneration. Here, we sought to prevent neurodegeneration in ALS/FTD models using selective inhibitor of nuclear export (SINE) compounds that target exportin-1 (XPO1)...
March 15, 2018: Scientific Reports
A Covarrubias-Pinto, A I Acuña, G Boncompain, E Pápic, P V Burgos, F Perez, M A Castro
Ascorbic acid (Asc) is an antioxidant molecule essential for physiological functions. The concentration of extracellular Asc increases during synaptic transmission and renal reabsorption. These phenomena induce an increase of the Sodium-dependent-Vitamin-C-transporter 2 (SVCT2) at plasma membrane (PM) localization, as we previously demonstrated in neuronal and non-neuronal cells. Hence, the aim of this study was to evaluate intracellular SVCT2 trafficking kinetics in response to Asc. We observed two peaks of SVCT2 localization and function at the PM (at 5-10min, "acute response", and 30-60min, "post-acute response") when cells were incubated with Asc...
March 12, 2018: Free Radical Biology & Medicine
Lisa K Gouwens, Mudar S Ismail, Victoria A Rogers, Nathan T Zeller, Evan C Garrad, Fatima S Amtashar, Nyasha J Makoni, David C Osborn, Michael R Nichols
Microvesicles (MVs) and exosomes comprise a class of cell-secreted particles termed extracellular vesicles (EVs). These cargo-holding vesicles mediate cell-to-cell communication and have recently been implicated in neurodegenerative diseases such as Alzheimer's disease (AD). The two types of EVs are distinguished by the mechanism of cell release and their size, with the smaller exosomes and the larger MVs ranging from 30 to 100 nm and 100 nm to 1 μm in diameter, respectively. MV numbers are increased in AD and appear to interact with amyloid-β peptide (Aβ), the primary protein component of the neuritic plaques in the AD brain...
March 15, 2018: ACS Chemical Neuroscience
Thomas O Tolsma, Lena M Cuevas, Santiago M Di Pietro
Clathrin mediated endocytosis is a fundamental transport pathway that depends on numerous protein-protein interactions. Testing the importance of the adaptor protein-clathrin interaction for coat formation and progression of endocytosis in vivo has been difficult due to experimental constrains. Here we addressed this question using the yeast clathrin adaptor Sla1, which is unique in showing a cargo endocytosis defect upon substitution of three amino acids in its clathrin-binding motif (sla1AAA ) that disrupt clathrin binding...
March 15, 2018: Traffic
Kristie Wrasman, Salvatore L Alioto, Yorke Zhang, Kyle Hoban, Marjon Khairy, Bruce L Goode, Beverly Wendland
Endocytosis is a fundamental process for internalizing material from the plasma membrane, including many transmembrane proteins that are selectively internalized depending on environmental conditions. In most cells, the main route of entry is clathrin-mediated endocytosis (CME), a process that involves the coordinated activity of over 60 proteins; however, there are likely as-yet unidentified proteins involved in cargo selection and/or regulation of endocytosis. We performed a mutagenic screen to identify novel endocytic genes in Saccharomyces cerevisiae expressing the methionine permease Mup1 tagged with pHluorin (pHl), a pH-sensitive GFP variant whose fluorescence is quenched upon delivery to the acidic vacuole lumen...
March 14, 2018: G3: Genes—Genomes—Genetics
Richard S Marshall, Richard D Vierstra
Plants have evolved sophisticated mechanisms to recycle intracellular constituents, which are essential for developmental and metabolic transitions; for efficient nutrient reuse; and for the proper disposal of proteins, protein complexes, and even entire organelles that become obsolete or dysfunctional. One major route is autophagy, which employs specialized vesicles to encapsulate and deliver cytoplasmic material to the vacuole for breakdown. In the past decade, the mechanics of autophagy and the scores of components involved in autophagic vesicle assembly have been documented...
March 14, 2018: Annual Review of Plant Biology
Yingqian Peng, Edouard Baulier, Yifeng Ke, Alejandra Young, Novruz B Ahmedli, Steven D Schwartz, Debora B Farber
Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions...
2018: PloS One
Xiaobin Xu, Shuang Hou, Natcha Wattanatorn, Fang Wang, Qing Yang, Chuanzhen Zhao, Xiao Yu, Hsian-Rong Tseng, Steven J Jonas, Paul S Weiss
An efficient nonviral platform for high-throughput and subcellular precision targeted intracellular delivery of nucleic acids in cell culture based on magnetic nanospears is reported. These magnetic nanospears are made of Au/Ni/Si (∼5 μm in length with tip diameters <50 nm) and fabricated by nanosphere lithography and metal deposition. A magnet is used to direct the mechanical motion of a single nanospear, enabling precise control of position and three-dimensional rotation. These nanospears were further functionalized with enhanced green fluorescent protein (eGFP)-expression plasmids via a layer-by-layer approach before release from the underlying silicon substrate...
March 14, 2018: ACS Nano
Tanaya Vaidya, Robert M Straubinger, Sihem Ait-Oudhia
PURPOSE: Trastuzumab combined with Doxorubicin (DOX) demonstrates significant clinical activity in human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC). However, emergence of treatment resistance and trastuzumab associated cardiotoxicity remain clinical challenges. In an effort to improve patient outcome, we have developed and evaluated novel tri-functional immunoliposomes (TFIL) that target HER2-receptors on BC cells and CD3-receptors on T-lymphocytes, and deliver DOX...
March 13, 2018: Pharmaceutical Research
Bo Hou, Eyleen S Heidrich, Denise Mehner-Breitfeld, Thomas Brüser
The twin-arginine translocation (Tat) system that comprises the TatA, TatB, and TatC components transports folded proteins across energized membranes of prokaryotes and plant plastids. It is not known, however, how the transport of this protein cargo is achieved. Favored models suggest that the TatA component supports transport by weakening the membrane upon full translocon assembly. Using Escherichia coli as model organism, we now demonstrate in vivo that the N-terminus of TatA can indeed destabilize the membrane, resulting in a lowered membrane energization in growing cells...
March 13, 2018: Journal of Biological Chemistry
Claudia Conte, Francesca Mastrotto, Vincenzo Taresco, Aleksandra Tchoryk, Fabiana Quaglia, Snjezana Stolnik, Cameron Alexander
In the treatment of lung cancer, there is an urgent need of innovative medicines to optimize pharmacological responses of conventional chemotherapeutics while attenuating side effects. Here, we have exploited some relatively unexplored subtle differences in reduction potential, associated with cancer cell microenvironments in addition to the well-known changes in intracellular redox environment. We report the synthesis and application of novel redox-responsive PLGA (poly(lactic-co-glycolic acid)) -PEG (polyethylene glycol) nanoparticles (RR-NPs) programmed to change surface properties when entering tumor microenvironments, thus enhance cell internalization of the particles and their drug cargo...
March 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Cher-Pheng Ooi, Terry K Smith, Eva Gluenz, Nadina Vasileva Wand, Sue Vaughan, Gloria Rudenko
The predominant secretory cargo of bloodstream form Trypanosoma brucei is Variant Surface Glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of ER exit sites (ERES) in post-mitotic cells dropped from (3...
March 13, 2018: Traffic
Uri Weill, Eric C Arakel, Omer Goldmann, Matan Golan, Silvia Chuartzman, Sean Munro, Blanche Schwappach, Maya Schuldiner
A third of yeast genes encode for proteins that function in the endomembrane system. However, the precise localization for many of these proteins is still uncertain. Here, we visualized a collection of ~500 N-terminally, green fluorescent protein (GFP), tagged proteins of the yeast Saccharomyces cerevisiae. By co-localizing them with seven known markers of endomembrane compartments we determined the localization for over 200 of them. Using this approach, we create a systematic database of the various secretory compartments and identify several new residents...
March 12, 2018: Traffic
Md Zahidul Islam, Sabrina Sharmin, Md Moniruzzaman, Masahito Yamazaki
Cell-penetrating peptides (CPPs) can translocate across the plasma membrane of living eukaryotic cells and enter the cytosol without significantly affecting cell viability. Consequently, CPPs have been used for the intracellular delivery of biological cargo such as proteins and oligonucleotides. However, the mechanisms underlying the translocation of CPPs across the plasma membrane remain unclear. In this mini-review, we summarize the experimental results regarding the entry of CPPs into lipid bilayer vesicles obtained using three methods: the large unilamellar vesicle (LUV) suspension method, the giant unilamellar vesicle (GUV) suspension method, and the single GUV method...
March 9, 2018: Applied Microbiology and Biotechnology
Mo Chen, Tao Qiu, Jiajie Wu, Yang Yang, Graham D Wright, Min Wu, Ruowen Ge
Classic endocytosis destinations include the recycling endosome returning to the plasma membrane or the late endosome (LE) merging with lysosomes for cargo degradation. However, the anti-angiogenic proteins angiostatin and isthmin, are endocytosed and trafficked to mitochondria (Mito) to execute apoptosis of endothelial cells. How these extracellular proteins reach mitochondria remains a mystery. Through confocal and super-resolution fluorescent microscopy, we demonstrate that angiostatin and isthmin are trafficked to mitochondria through the interaction between LE and Mito...
March 9, 2018: Cell Death and Differentiation
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