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https://www.readbyqxmd.com/read/27933291/endocytosis-and-physiology-insights-from-disabled-2-deficient-mice
#1
REVIEW
Wensi Tao, Robert Moore, Elizabeth R Smith, Xiang-Xi Xu
Disabled-2 (Dab2) is a clathrin and cargo binding endocytic adaptor protein, and cell biology studies revealed that Dab2 plays a role in cellular trafficking of a number of transmembrane receptors and signaling proteins. A PTB/PID domain located in the N-terminus of Dab2 binds the NPXY motif(s) present at the cytoplasmic tails of certain transmembrane proteins/receptors. The membrane receptors reported to bind directly to Dab2 include LDL receptor and its family members LRP1 and LRP2 (megalin), growth factor receptors EGFR and FGFR, and the cell adhesion receptor beta1 integrin...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27933272/autophagy-dependent-secretion-contribution-to-tumor-progression
#2
REVIEW
Tom G Keulers, Marco B E Schaaf, Kasper M A Rouschop
Autophagy is best known as a lysosomal degradation and recycling pathway to maintain cellular homeostasis. During autophagy, cytoplasmic content is recognized and packed in autophagic vacuoles, or autophagosomes, and targeted for degradation. However, during the last years, it has become evident that the role of autophagy is not restricted to degradation alone but also mediates unconventional forms of secretion. Furthermore, cells with defects in autophagy apparently are able to reroute their cargo, like mitochondria, to the extracellular environment; effects that contribute to an array of pathologies...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27932448/dedicated-snares-and-specialized-trim-cargo-receptors-mediate-secretory-autophagy
#3
Tomonori Kimura, Jingyue Jia, Suresh Kumar, Seong Won Choi, Yuexi Gu, Michal Mudd, Nicolas Dupont, Shanya Jiang, Ryan Peters, Farzin Farzam, Ashish Jain, Keith A Lidke, Christopher M Adams, Terje Johansen, Vojo Deretic
Autophagy is a process delivering cytoplasmic components to lysosomes for degradation. Autophagy may, however, play a role in unconventional secretion of leaderless cytosolic proteins. How secretory autophagy diverges from degradative autophagy remains unclear. Here we show that in response to lysosomal damage, the prototypical cytosolic secretory autophagy cargo IL-1β is recognized by specialized secretory autophagy cargo receptor TRIM16 and that this receptor interacts with the R-SNARE Sec22b to recruit cargo to the LC3-II(+) sequestration membranes...
December 8, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27930654/whole-organism-developmental-expression-profiling-identifies-rab-28-as-a-novel-ciliary-gtpase-associated-with-the-bbsome-and-intraflagellar-transport
#4
Victor L Jensen, Stephen Carter, Anna A W M Sanders, Chunmei Li, Julie Kennedy, Tiffany A Timbers, Jerry Cai, Noemie Scheidel, Breandán N Kennedy, Ryan D Morin, Michel R Leroux, Oliver E Blacque
Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa and Bardet-Biedl syndrome (BBS), frequently affecting many physiological and developmental processes across multiple organs. Cilium formation, maintenance and function depend on intracellular transport systems such as intraflagellar transport (IFT), which is driven by kinesin-2 and IFT-dynein motors and regulated by the Bardet-Biedl syndrome (BBS) cargo-adaptor protein complex, or BBSome...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27929705/snapin-is-critical-for-lysosomal-acidification-and-autophagosome-maturation-in-macrophages
#5
Bo Shi, Qi-Quan Huang, Robert Birkett, Renee Doyle, Andrea Dorfleutner, Christian Stehlik, Congcong He, Richard M Pope
We previously observed that SNAPIN, which is an adaptor protein in the SNARE core complex, was highly expressed in rheumatoid arthritis synovial tissue macrophages, but its role in macrophages and autoimmunity is unknown. To identify SNAPIN's role in these cells, we employed siRNA to silence the expression of SNAPIN in primary human macrophages. Silencing SNAPIN resulted in swollen lysosomes with impaired CTSD (cathepsin D) activation, although total CTSD was not reduced. Neither endosome cargo delivery nor lysosomal fusion with endosomes or autophagosomes was inhibited following the forced silencing of SNAPIN...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27928935/taking-the-stock-of-granule-cargo-platelet-releasate-proteomics
#6
Oliver Pagel, Elena Walter, Kerstin Jurk, René P Zahedi
Human platelets are key players in a multitude of physiological and pathological processes. Upon activation they release cargo from different types of granules as well as microparticles in an apparently well-regulated and orchestrated manner. The resulting specific platelet releasates create microenvironments of biologically active compounds and proteins during platelet aggregation and thrombus formation, allowing efficient delivery of growth factors and immune modulators to their sites of effect and enhancing the coagulative response in a positive feedback loop...
December 8, 2016: Platelets
https://www.readbyqxmd.com/read/27927751/rab2a-and-rab27a-cooperatively-regulate-transition-from-granule-maturation-to-exocytosis-through-the-dual-effector-noc2
#7
Kohichi Matsunaga, Masato Taoka, Toshiaki Isobe, Tetsuro Izumi
Exocytosis of secretory granules entails budding from the trans-Golgi network, sorting and maturation of cargo proteins, and trafficking and fusion to the plasma membrane. Rab27a regulates the late steps in this process, such as granule recruitment to the fusion site, whereas Rab2a functions in the early steps, such as granule biogenesis and maturation. Here, we demonstrate that these two small GTPases simultaneously bind to Noc2 in GTP-dependent manners, although Rab2a binds only after Rab27a has bound. In pancreatic beta cells, the ternary Rab2a-Noc2-Rab27a complex specifically localizes on perinuclear immature granules, whereas the binary Noc2-Rab27a complex localizes on peripheral mature granules...
December 7, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27923197/single-chain-fc-dimer-human-growth-hormone-fusion-protein-for-improved-drug-delivery
#8
Li Zhou, Hsuan-Yao Wang, Shanshan Tong, Curtis T Okamoto, Wei-Chiang Shen, Jennica L Zaro
Fc fusion protein technology has been successfully used to generate long-acting forms of several protein therapeutics. In this study, a novel Fc-based drug carrier, single chain Fc-dimer (sc(Fc)2), was designed to contain two Fc domains recombinantly linked via a flexible linker. Since the Fc dimeric structure is maintained through the flexible linker, the hinge region was omitted to further stabilize it against proteolysis and reduce FcγR-related effector functions. The resultant sc(Fc)2 candidate preserved the neonatal Fc receptor (FcRn) binding...
November 27, 2016: Biomaterials
https://www.readbyqxmd.com/read/27921095/journey-from-the-center-of-the-cell-the-intra-and-intercellular-transport-of-mrna
#9
Anna Kasprowicz-Maluśki, Wojciech Kwiatkowski, Alicja Starosta, Przemysław Wojtaszek
Transport and localized translation of mRNA is crucial for the proper spatiotemporal organization of proteins within cells. Distribution of RNAs to subcellular domains has recently emerged as a major mechanism for establishing functionally distinct compartments and structures in the cells. There is an emerging evidence that active transport of mRNA involves cytoskeleton and membrane trafficking pathways in fungi, plants and animals, suggesting that it is a common phenomenon among eukaryotes. The important highlights are that the RNA-binding proteins recognize the cargo mRNA and that RNPs are actively transported on the cytoskeletal tracks or co-transported with membranous compartments, such as the endoplasmic reticulum and endosomes...
December 6, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27921011/mechanisms-of-infectivity-and-evasion-derived-from-microvesicles-cargo-produced-by-trypanosoma-cruzi
#10
REVIEW
Bruna C Borges, Isadora A Uehara, Laysa O S Dias, Paula C Brígido, Claudio V da Silva, Marcelo J B Silva
Cell invasion by the intracellular protozoans requires interaction of proteins from both the host and the parasite. Many parasites establish chronic infections, showing they have the potential to escape the immune system; for example, Trypanosoma cruzi is an intracellular parasite that causes Chagas disease. Parasite internalization into host cell requires secreted and surface molecules, such as microvesicles. The release of microvesicles and other vesicles, such as exosomes, by different eukaryotic organisms was first observed in the late twentieth century...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27919066/designed-proteins-induce-the-formation-of-nanocage-containing-extracellular-vesicles
#11
Jörg Votteler, Cassandra Ogohara, Sue Yi, Yang Hsia, Una Nattermann, David M Belnap, Neil P King, Wesley I Sundquist
Complex biological processes are often performed by self-organizing nanostructures comprising multiple classes of macromolecules, such as ribosomes (proteins and RNA) or enveloped viruses (proteins, nucleic acids and lipids). Approaches have been developed for designing self-assembling structures consisting of either nucleic acids or proteins, but strategies for engineering hybrid biological materials are only beginning to emerge. Here we describe the design of self-assembling protein nanocages that direct their own release from human cells inside small vesicles in a manner that resembles some viruses...
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27917875/exploring-experimental-cerebral-malaria-pathogenesis-through-the-characterisation-of-host-derived-plasma-microparticle-protein-content
#12
Natalia Tiberti, Sharissa L Latham, Stephen Bush, Amy Cohen, Robert O Opoka, Chandy C John, Annette Juillard, Georges E Grau, Valéry Combes
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection responsible for thousands of deaths in children in sub-Saharan Africa. CM pathogenesis remains incompletely understood but a number of effectors have been proposed, including plasma microparticles (MP). MP numbers are increased in CM patients' circulation and, in the mouse model, they can be localised within inflamed vessels, suggesting their involvement in vascular damage. In the present work we define, for the first time, the protein cargo of MP during experimental cerebral malaria (ECM) with the overarching hypothesis that this characterisation could help understand CM pathogenesis...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27913308/biodegradable-magnetic-silica-iron-oxide-nanovectors-with-ultra-large-mesopores-for-high-protein-loading-magnetothermal-release-and-delivery
#13
Haneen Omar, Jonas G Croissant, Kholod Alamoudi, Shahad Alsaiari, Ibrahim Alradwan, Majed A Majrashi, Dalaver H Anjum, Patricia Martins, Basem Moosa, Abdulaziz Almalik, Niveen M Khashab
The delivery of large cargos of diameter above 15nm for biomedical applications has proved challenging since it requires biocompatible, stably-loaded, and biodegradable nanomaterials. In this study, we describe the design of biodegradable silica-iron oxide hybrid nanovectors with large mesopores for large protein delivery in cancer cells. The mesopores of the nanomaterials spanned from 20 to 60nm in diameter and post-functionalization allowed the electrostatic immobilization of large proteins (e.g. mTFP-Ferritin, ~534kDa)...
November 29, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27912878/selecting-optimum-protein-nano-carriers-for-natural-polyphenols-using-chemoinformatics-tools
#14
AbdelKader A Metwally, Sherweit H El-Ahmady, Rania M Hathout
BACKGROUND: The normal fate of any natural product with a therapeutic potential is to be formulated into an effective medicine. However, the conventional methods of selecting the suitable formulations or carriers based on the formulator experiences, trials and errors as well as materials availability do not usually yield the optimal results. HYPOTHESIS: We hypothesize the possibility of the virtual optimum selection of a protein carrier for two polyphenolic compounds widely investigated for their chemopreventive effects; resveratrol and curcumin using a combination of some chemoinformatics tools...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27911709/shuttling-and-sorting-lipid-modified-cargo-into-the-cilia
#15
REVIEW
Louise A Stephen, Shehab Ismail
Primary cilia are hair-like microtubule-based organelles that can be found on almost all human cell types. Although the cilium is not separated from the cell by membranes, their content is different from that of the cell body and their membrane composition is distinct from that of the plasma membrane. Here, we will introduce a molecular machinery that shuttles and sorts lipid-modified proteins to the cilium, thus contributing in maintaining its distinct composition. The mechanism involves the binding of the GDI-like solubilising factors, uncoordinated (UNC)119a, UNC119b and PDE6D, to the lipid-modified ciliary cargo and the specific release of the cargo in the cilia by the ciliary small G-protein Arl3 in a GTP-dependent manner...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911359/directed-protein-packaging-within-outer-membrane-vesicles-from-escherichia-coli-design-production-and-purification
#16
Nathan J Alves, Kendrick B Turner, Scott A Walper
An increasing interest in applying synthetic biology techniques to program outer membrane vesicles (OMV) are leading to some very interesting and unique applications for OMV where traditional nanoparticles are proving too difficult to synthesize. To date, all Gram-negative bacteria have been shown to produce OMV demonstrating packaging of a variety of cargo that includes small molecules, peptides, proteins and genetic material. Based on their diverse cargo, OMV are implicated in many biological processes ranging from cell-cell communication to gene transfer and delivery of virulence factors depending upon which bacteria are producing the OMV...
November 16, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27909246/retromer-wash-dependent-sorting-of-nutrient-transporters-requires-a-multivalent-interaction-network-with-ankrd50
#17
Arunas Kvainickas, Ana Jimenez Orgaz, Heike Nägele, Britta Diedrich, Kate J Heesom, Jörn Dengjel, Peter J Cullen, Florian Steinberg
Retromer and the associated actin polymerizing WASH-complex are essential for the endocytic recycling of a wide range of integral membrane proteins. A hereditary Parkinson's disease causing point mutation (D620N) in the retromer subunit VPS35 perturbs retromer's association with the WASH-complex and also with the uncharacterized protein Ankyrin Repeat Domain Containing Protein 50 (ANKRD50). Here, we firmly establish ANKRD50 as a novel and essential component of the SNX27-retromer-WASH supercomplex. Depletion of ANKRD50 in HeLa or U2OS cells phenocopied the loss of endosome to cell surface recycling of multiple transmembrane proteins seen upon suppression of SNX27, retromer or WASH-complex components...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27906043/exosomes-play-an-important-role-in-the-process-of-psoralen-reverse-multidrug-resistance-of-breast-cancer
#18
Xiaohong Wang, Chengfeng Xu, Yitong Hua, Leitao Sun, Kai Cheng, Zhongming Jia, Yong Han, Jianli Dong, Yuzhen Cui, Zhenlin Yang
BACKGROUND: Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance. METHOD: In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo)...
December 1, 2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27903609/protein-sorting-at-the-er-golgi-interface
#19
REVIEW
Natalia Gomez-Navarro, Elizabeth Miller
Protein traffic is of critical importance for normal cellular physiology. In eukaryotes, spherical transport vesicles move proteins and lipids from one internal membrane-bound compartment to another within the secretory pathway. The process of directing each individual protein to a specific destination (known as protein sorting) is a crucial event that is intrinsically linked to vesicle biogenesis. In this review, we summarize the principles of cargo sorting by the vesicle traffic machinery and consider the diverse mechanisms by which cargo proteins are selected and captured into different transport vesicles...
November 30, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27903455/complexation-hydrogels-as-potential-carriers-in-oral-vaccine-delivery-systems
#20
Mia Yoshida, Noriyasu Kamei, Keiya Muto, Jun Kunisawa, Kozo Takayama, Nicholas A Peppas, Mariko Takeda-Morishita
Most current vaccine preparations are in injectable forms, which are inconvenient to patients and ineffective in mucosal immunization. Therefore, most research in this field has been directed at developing ideal oral vaccines enabling the induction of both systemic and mucosal immune responses. In the present study, we examined the utility of a pH-responsive polymeric carrier, poly (methacrylic acid-g-ethylene glycol) [P (MAA-g-EG)] hydrogel, as a potential oral vaccine carrier that can protect cargo proteins in the gastrointestinal tract...
November 26, 2016: European Journal of Pharmaceutics and Biopharmaceutics
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