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https://www.readbyqxmd.com/read/29777875/switching-cell-penetrating-and-cxcr4-binding-activities-of-nanoscale-organized-arginine-rich-peptides
#1
Marianna Teixeira de Pinho Favaro, Naroa Serna, Laura Sánchez-García, Rafael Cubarsi, Mónica Roldán, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón Mangues, Neus Ferrer-Miralles, Adriano Rodrigues Azzoni, Esther Vázquez, Antonio Villaverde
Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown...
May 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29777705/membrane-proteins-significantly-restrict-exosome-mobility
#2
Mikhail Skliar, Vasiliy S Chernyshev, David M Belnap, German V Sergey, Samer M Al-Hakami, Philip S Bernard, Inge J Stijleman, Rakesh Rachamadugu
Exosomes are membrane nanovesicles implicated in cell-to-cell signaling in which they transfer their molecular cargo from the parent to the recipient cells. This role essentially depends on the exosomes' small size, which is the prerequisite for their rapid migration through the crowded extracellular matrix and into and out of circulation. Here we report much lower exosome mobility than expected from the size of their vesicles, implicate membrane proteins in a substantially impeded rate of migration, and suggest an approach to quantifying the impact...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777103/bacterial-encapsulins-as-orthogonal-compartments-for-mammalian-cell-engineering
#3
Felix Sigmund, Christoph Massner, Philipp Erdmann, Anja Stelzl, Hannes Rolbieski, Mitul Desai, Sarah Bricault, Tobias P Wörner, Joost Snijder, Arie Geerlof, Helmut Fuchs, Martin Hrabĕ de Angelis, Albert J R Heck, Alan Jasanoff, Vasilis Ntziachristos, Jürgen Plitzko, Gil G Westmeyer
We genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-constrained metal biomineralization. The shell protein (EncA) from Myxococcus xanthus auto-assembles into nanocompartments inside mammalian cells to which sets of native (EncB,C,D) and engineered cargo proteins self-target enabling localized bimolecular fluorescence and enzyme complementation. Encapsulation of the enzyme tyrosinase leads to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT)...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777037/inhibition-of-tbc1d5-activates-rab7a-and-can-enhance-the-function-of-the-retromer-cargo-selective-complex
#4
Matthew N J Seaman, Aamir S Mukadam, Sophia Y Breusegem
The retromer complex is a vital component of the endosomal protein sorting machinery being necessary for sorting into both the endosome-to-Golgi retrieval pathway and also the endosome-to-cell-surface recycling pathway. Retromer mediates cargo selection through a trimeric complex comprising VPS35, VPS29 and VPS26 which is recruited to endosomes by binding to Rab7a and Snx3. Retromer function is linked to two distinct neurodegenerative diseases, Parkinson's disease and Alzheimer's disease and modulating retromer function has been proposed as an avenue to explore for a putative therapy in these conditions...
May 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29774507/ap180-n-terminal-homology-anth-and-epsin-n-terminal-homology-enth-domains-physiological-functions-and-involvement-in-disease
#5
Sho Takatori, Taisuke Tomita
The AP180 N-terminal homology (ANTH) and Epsin N-terminal homology (ENTH) domains are crucially involved in membrane budding processes. All the ANTH/ENTH-containing proteins share the phosphoinositide-binding activity and can interact with clathrin or its related proteins via multiple binding motifs. Their function also include promotion of clathrin assembly, induction of membrane curvature, and recruitment of various effector proteins, such as those involved in membrane fission. Furthermore, they play a role in the sorting of specific cargo proteins, thereby enabling the cargos to be accurately transported and function at their appropriate locations...
May 18, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29774070/role-of-extracellular-vesicles-in-viral-and-bacterial-infections-pathogenesis-diagnostics-and-therapeutics
#6
REVIEW
Meryl Rodrigues, Jia Fan, Christopher Lyon, Meihua Wan, Ye Hu
Extracellular vesicles (EVs), or exosomes, are nanovesicles of endocytic origin that carry host and pathogen-derived protein, nucleic acid, and lipid cargos. They are secreted by most cell types and play important roles in normal cell-to-cell communications but can also spread pathogen- and host-derived molecules during infections to alter immune responses and pathophysiological processes. New research is beginning to decipher how EVs influence viral and bacterial pathogenesis. In this review, we will describe how EVs influence viral and bacterial pathogenesis by spreading pathogen-derived factors and how they can promote and inhibit the immune response to these pathogens...
2018: Theranostics
https://www.readbyqxmd.com/read/29773651/usp25m-protease-regulates-ubiquitin-like-processing-of-tug-proteins-to-control-glut4-glucose-transporter-translocation-in-adipocytes
#7
Estifanos N Habtemichael, Don T Li, Abel Alcázar-Román, Xavier O Westergaard, Muyi Li, Max C Petersen, Hanbing Li, Stephen G DeVries, Eric Li, Omar Julca-Zevallos, Joseph S Wolenski, Jonathan S Bogan
Insulin stimulates the exocytic translocation of specialized vesicles in adipocytes, which inserts GLUT4 glucose transporters into the plasma membrane to enhance glucose uptake.  Previous results support a model in which TUG proteins trap these GLUT4 storage vesicles at the Golgi matrix, and in which insulin triggers endoproteolytic cleavage of TUG to translocate GLUT4.  Here, we identify Usp25m as a protease required for insulin-stimulated TUG cleavage and GLUT4 translocation in adipocytes.  Usp25m is expressed in adipocytes, binds TUG and GLUT4, dissociates from TUG-bound vesicles after insulin addition, and colocalizes with TUG and insulin-responsive cargoes in unstimulated cells...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29760422/sculpting-and-fusing-biomimetic-vesicle-networks-using-optical-tweezers
#8
Guido Bolognesi, Mark S Friddin, Ali Salehi-Reyhani, Nathan E Barlow, Nicholas J Brooks, Oscar Ces, Yuval Elani
Constructing higher-order vesicle assemblies has discipline-spanning potential from responsive soft-matter materials to artificial cell networks in synthetic biology. This potential is ultimately derived from the ability to compartmentalise and order chemical species in space. To unlock such applications, spatial organisation of vesicles in relation to one another must be controlled, and techniques to deliver cargo to compartments developed. Herein, we use optical tweezers to assemble, reconfigure and dismantle networks of cell-sized vesicles that, in different experimental scenarios, we engineer to exhibit several interesting properties...
May 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29759379/simultaneous-surface-display-and-cargo-loading-of-encapsulin-nanocompartments-and-their-use-for-rational-vaccine-design
#9
Priscillia Lagoutte, Charlotte Mignon, Gustavo Stadthagen, Supanee Potisopon, Stéphanie Donnat, Jan Mast, Adrien Lugari, Bettina Werle
In the past decades protein nanoparticles have successfully been used for vaccine applications. Their particulate nature and dense repetitive subunit organization makes them perfect carriers for antigen surface display and confers high immunogenicity. Nanoparticles have emerged as excellent candidates for vectorization of biological and immunostimulating molecules. Nanoparticles and biomolecular nanostructures such as ferritins or virus like particles have been used as diagnostic and therapeutic delivery systems, in vaccine development, as nanoreactors, etc...
May 11, 2018: Vaccine
https://www.readbyqxmd.com/read/29758299/autophagy-regulates-apoptosis-by-targeting-noxa-for-degradation
#10
Jingchao Wang, Danrui Cui, Shanshan Gu, Xiaoyu Chen, Yanli Bi, Xiufang Xiong, Yongchao Zhao
Apoptosis and autophagy mutually regulate various cellular physiological and pathological processes. The crosstalk between autophagy and apoptosis is multifaceted and complicated. Elucidating the molecular mechanism of their crosstalk will advance the therapeutic applications of autophagy for treating cancer and other diseases. NOXA, a BH3-only member of the BCL-2 family, was reported to induce apoptosis and promote autophagy. Here, we report that autophagy regulates apoptosis by targeting NOXA for degradation...
May 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29755357/-n-glycosylation-of-lipocalin-2-is-not-required-for-secretion-or-exosome-targeting
#11
Erawan Borkham-Kamphorst, Eddy Van de Leur, Steffen K Meurer, Eva M Buhl, Ralf Weiskirchen
Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids. In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota. Human LCN2 contains one N -glycosylation site conserved in other species. It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29755290/retromer-dysfunction-and-neurodegenerative-disease
#12
REVIEW
Christiane Reitz
In recent years, genomic, animal and cell biology studies have implicated deficiencies in retromer-mediated trafficking of proteins in an increasing number of neurodegenerative diseases including Alzheimer's Disease (AD), Parkinson's Disease (PD) and Frontotemporal Lobar Degener-ation (FTLD). The retromer complex, which is highly conserved across all eukaryotes, regulates the sorting of transmembrane proteins out of endo-somes to the cell surface or to the trans-Golgi network. Within retromer, cargo selection and binding are performed by a trimer of the Vps26, Vps29 and Vps35 proteins, named the "Cargo-Selective Complex (CSC)"...
May 2018: Current Genomics
https://www.readbyqxmd.com/read/29751226/plasmodesmata-in-phloem-different-gateways-for-different-cargoes
#13
REVIEW
Jung-Youn Lee, Margaret Frank
The long-distance transport of sugars and nutrients through the phloem is essential for the proper function and growth of vascular plants. However, in addition to essential nutrients and sugars, phloem sap also contains small molecules (e.g. hormones) as well as a diverse population of macromolecules (i.e. proteins small RNAs, and mRNAs), the endogenous functions of which remain largely unknown. Understanding the cellular origins of these mobile macromolecules, their path into and out of the phloem translocation stream, and their fate at their new destination is essential for characterizing their presumptive function...
May 8, 2018: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/29750988/contribution-of-the-residue-at-position-4-within-classical-nuclear-localization-signals-to-modulating-interaction-with-importins-and-nuclear-targeting
#14
Kate M Smith, Veronica Di Antonio, Luca Bellucci, David R Thomas, Fabiana Caporuscio, Francesco Ciccarese, Hanieh Ghassabian, Kylie M Wagstaff, Jade K Forwood, David A Jans, Giorgio Palù, Gualtiero Alvisi
Nuclear import involves the recognition by importin (IMP) superfamily members of nuclear localization signals (NLSs) within protein cargoes destined for the nucleus, the best understood being recognition of classical NLSs (cNLSs) by the IMPα/β1 heterodimer. Although the cNLS consensus [K-(K/R)-X-(K/R) for positions P2-P5] is generally accepted, recent studies indicated that the contribution made by different residues at the P4 position can vary. Here, we apply a combination of microscopy, molecular dynamics, crystallography, in vitro binding, and bioinformatics approaches to show that the nature of residues at P4 indeed modulates cNLS function in the context of a prototypical Simian Virus 40 large tumor antigen-derived cNLS (KKRK, P2-5)...
May 8, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29748909/the-effect-of-storage-temperature-on-the-biological-activity-of-extracellular-vesicles-for-the-complement-system
#15
Sang June Park, Hyungtaek Jeon, Seung-Min Yoo, Myung-Shin Lee
Extracellular vesicles (EVs) are mediators of intercellular communication by transporting cargo containing proteins, lipids, mRNA, and miRNA. There is increasing evidence that EVs have various roles in regulating migration, invasion, stemness, survival, and immune functions. Previously, we have found that EVs from Kaposi's sarcoma-associated herpesvirus (KSHV)-infected human endothelial cells have the potential to activate the complement system. Although many studies have shown that the physical properties of EVs can be changed by their storage condition, there have been few studies for the stability of biological activity of EVs in various storage conditions...
May 10, 2018: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/29746864/drug-delivery-using-polyhistidine-peptide-modified-liposomes-that-target-the-endogenous-lysosome
#16
Taiki Hayashi, Matsumi Shinagawa, Tsuyoshi Kawano, Takashi Iwasaki
Cell-penetrating peptides (CPPs) can deliver payloads into cells by forming complexes with bioactive molecules via covalent or non-covalent bonds. Various CPPs have been applied in CPP-modified liposomes, and their effectiveness is highly regarded in liposomal drug delivery systems (DDSs). Previously, we have reported on the polyhistidine peptide (H16 peptide: HHHHHHHHHHHHHHHH-NH2 ) as a new CPP. The H16 peptide has a higher cell-penetrating capacity than well-known CPPs and delivers small molecules such as fluorescent dyes, bioactive peptides, and proteins into mammalian cells...
May 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29743505/contrasting-roles-for-actin-in-the-cellular-uptake-of-cell-penetrating-peptide-conjugates
#17
L He, E J Sayers, P Watson, A T Jones
The increased need for macromolecular therapeutics, such as peptides, proteins and nucleotides, to reach intracellular targets necessitates more effective delivery vectors and a higher level of understanding of their mechanism of action. Cell penetrating peptides (CPPs) can transport a range of macromolecules into cells, either through direct plasma membrane translocation or endocytosis. All known endocytic pathways involve cell-cortex remodelling, a process shown to be regulated by reorganisation of the actin cytoskeleton...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29743203/the-parkinson-s-disease-vps35-d620n-mutation-enhances-lrrk2-mediated-rab-protein-phosphorylation-in-mouse-and-human
#18
Rafeeq Mir, Francesca Tonelli, Pawel Lis, Thomas Macartney, Nicole K Polinski, Terina N Martinez, Meng-Yun Chou, Andrew J M Howden, Theresa König, Christoph Hotzy, Ivan Milenkovic, Thomas Brücke, Alexander Zimprich, Esther Sammler, Dario R Alessi
Missense mutations in the LRRK2 and VPS35 genes result in autosomal dominant Parkinson's disease. The VPS35 gene encodes for the cargo-binding component of the retromer complex, while LRRK2 modulates vesicular trafficking by phosphorylating a subgroup of Rab proteins. Pathogenic mutations in LRRK2 increase its kinase activity. It is not known how the only thus far described pathogenic VPS35 mutation, [D620N] exerts its effects. We reveal that the VPS35[D620N] knock-in mutation, strikingly elevates LRRK2 mediated phosphorylation of Rab8A, Rab10 and Rab12 in mouse embryonic fibroblasts...
May 9, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29742343/hierarchical-assembly-of-sirna-with-tetraamino-fullerene-in-physiological-conditions-for-efficient-internalization-into-cells-and-knockdown
#19
Kosuke Minami, Koji Okamoto, Koji Harano, Eisei Noiri, Eiichi Nakamura
Delivery of siRNA is a key technique in alternative gene therapy, where the siRNA cargo must be effectively loaded onto a tailor-designed carrier molecule and smoothly unloaded precisely upon arrival at the target cells or organs. Any toxicity issues also need to be mitigated by suitable choice of the carrier molecule. A water-soluble cationic fullerene, tetra(piperazino)[60]fullerene epoxide (TPFE), was previously shown to be nontoxic and effective for lung-targeted in vivo siRNA delivery by way of agglutination-induced accumulation...
May 9, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29740045/exosome-markers-associated-with-immune-activation-and-oxidative-stress-in-hiv-patients-on-antiretroviral-therapy
#20
Sukrutha Chettimada, David R Lorenz, Vikas Misra, Simon T Dillon, R Keith Reeves, Cordelia Manickam, Susan Morgello, Gregory D Kirk, Shruti H Mehta, Dana Gabuzda
Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics...
May 8, 2018: Scientific Reports
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