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https://www.readbyqxmd.com/read/28641559/a-stepwise-approach-for-the-isolation-and-the-identification-of-chemically-reactive-exofacial-protein-thiols
#1
Gabriele Candiani, Elisa Fasoli
The plasma membrane controls the selective internalization of (macro)molecules through different mechanisms, often relaying on specialized outward-facing carriers such as exofacial proteins thiols (EPTs). Although the interchange of critical thiols and disulphides between EPTs and exogenous cargoes is the first critical event, the identification of specific cell interactors remains to be thoroughly explored. We herein devise an enabling methodology for the isolation and identification of a subset of EPTs, named chemically reactive EPS, which are potential theranostic targets...
June 20, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28638822/extracellular-vesicles-in-renal-pathophysiology
#2
REVIEW
Margherita A C Pomatto, Chiara Gai, Benedetta Bussolati, Giovanni Camussi
Extracellular vesicles are a heterogeneous population of microparticles released by virtually all living cells which have been recently widely investigated in different biological fields. They are typically composed of two primary types (exosomes and microvesicles) and are recently commanding increasing attention as mediators of cellular signaling. Indeed, these vesicles can affect recipient cells by carrying and delivering complex cargos of biomolecules (including proteins, lipids and nucleic acids), protected from enzymatic degradation in the environment...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28636979/exosomes-in-diagnosis-and-therapy-of-prostate-cancer
#3
REVIEW
Jun Pan, Meng Ding, Kai Xu, Chunhua Yang, Li-Jun Mao
Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the cargos of exosomes such as miRNAs, lncRNAs and proteins...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635326/encapsulins-molecular-biology-of-the-shell
#4
Robert J Nichols, Caleb Cassidy-Amstutz, Thawatchai Chaijarasphong, David F Savage
Compartmentalization is both a fundamental principle of cellular organization and an emerging theme in prokaryotic biology. Work in the past few decades has shown that protein-based organelles called microcompartments enhance the function of encapsulated cargo proteins. More recently, the repertoire of known prokaryotic organelles has expanded beyond microcompartments to include a new class of smaller proteinaceous compartments, termed nanocompartments (also known as encapsulins). Nanocompartments are icosahedral capsids that are smaller and less complex than microcompartments...
June 21, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28634871/rabies-virus-co-localizes-with-early-rab5-and-late-rab7-endosomal-proteins-in-neuronal-and-sh-sy5y-cells
#5
Waqas Ahmad, Yingying Li, Yidi Guo, Xinyu Wang, Ming Duan, Zhenhong Guan, Zengshan Liu, Maolin Zhang
Rabies virus (RABV) is a highly neurotropic virus that follows clathrin-mediated endocytosis and pH-dependent pathway for trafficking and invasion into endothelial cells. Early (Rab5, EEA1) and late (Rab7, LAMP1) endosomal proteins play critical roles in endosomal sorting, maturity and targeting various molecular cargoes, but their precise functions in the early stage of RABV neuronal infection remain elusive. In this study, the relationship between enigmatic entry of RABV with these endosomal proteins into neuronal and SH-SY5Y cells was investigated...
June 16, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/28634138/intracellular-and-transdermal-protein-delivery-mediated-by-non-covalent-interactions-with-a-synthetic-guanidine-rich-molecular-carrier
#6
Jungkyun Im, Sanket Das, Dongjun Jeong, Chang-Jin Kim, Hyun-Suk Lim, Ki Hean Kim, Sung-Kee Chung
The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins...
June 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28633594/targeting-and-delivery-of-therapeutic-enzymes
#7
Scott N Dean, Kendrick B Turner, Igor L Medintz, Scott A Walper
Biotechnology has revolutionized therapeutics for the treatment of a wide range of diseases. Recent advances in protein engineering and material science have made the targeted delivery of enzyme therapeutics using nanocarriers (NCs) a new model of treatment. Several NCs have been approved for clinical use in drug delivery. Despite their advantages, few NCs have been approved to deliver enzyme cargo in a targeted manner. This review details the current arsenal of platforms developed to deliver enzyme therapeutics as well as the advantages and challenges of using enzymes as drugs, with examples from the literature, and discusses the benefits and liabilities of a given approach...
July 2017: Therapeutic Delivery
https://www.readbyqxmd.com/read/28622586/outerwear-through-the-ages-evolutionary-cell-biology-of-vesicle-coats
#8
REVIEW
Joel B Dacks, Margaret S Robinson
Vesicular transport was key to the evolution of eukaryotes, and is essential for eukaryotic life today. All modern eukaryotes have a set of vesicle coat proteins, which couple cargo selection to vesicle budding in the secretory and endocytic pathways. Although these coats share common features (e.g. recruitment via small GTPases, β-propeller-α-solenoid proteins acting as scaffolds), the relationships between them are not always clear. Structural studies on the coats themselves, comparative genomics and cell biology in diverse eukaryotes, and the recent discovery of the Asgard archaea and their 'eukaryotic signature proteins' are helping us to piece together how coats may have evolved during the prokaryote-to-eukaryote transition...
June 13, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28619825/spef2-functions-in-microtubule-mediated-transport-in-elongating-spermatids
#9
Mari S Lehti, Fu-Ping Zhang, Noora Kotaja, Anu Sironen
Sperm differentiation requires specific protein transport for correct sperm tail formation and head shaping. A transient microtubular structure, the manchette, appears around the differentiating spermatid head and serves as a platform for protein transport to the growing tail. Sperm flagellar protein 2 (SPEF2) is known to be essential for sperm tail development. In this study we investigated the function of SPEF2 during spermatogenesis using a male germ cell-specific Spef2 knockout mouse model. In addition to defects in sperm tail development, we observed a duplication of the basal body and failure in the manchette migration resulting in an abnormal head shape...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28619261/sequestosome-1-sqstm1-p62-maintains-protein-folding-capacity-under-endoplasmic-reticulum-stress-in-mouse-hypothalamic-organotypic-culture
#10
Takashi Tominaga, Motomitsu Goto, Takeshi Onoue, Akira Mizoguchi, Mariko Sugiyama, Taku Tsunekawa, Daisuke Hagiwara, Yoshiaki Morishita, Yoshihiro Ito, Shintaro Iwama, Hidetaka Suga, Ryoichi Banno, Hiroshi Arima
Sequestosome 1 (SQSTM1) also known as ubiquitin-binding protein p62 (p62) is a cargo protein involved in the degradation of misfolded proteins via selective autophagy. Disruption of autophagy and resulting accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress. ER stress is implicated in several neurodegenerative diseases and obesity. As knockout of p62 (p62KO) reportedly induces obesity in mice, we examined how p62 contributes to ER stress and the ensuing unfolded protein response (UPR) in hypothalamus using mouse organotypic cultures in the present study...
June 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28615454/cytosolic-iron-chaperones-proteins-delivering-iron-cofactors-in-the-cytosol-of-mammalian-cells
#11
Caroline C Philpott, Moon-Suhn Ryu, Avery G Frey, Sarju Patel
Eukaryotic cells contain hundreds of metalloproteins that are supported by intracellular systems coordinating the uptake and distribution of metal cofactors. Iron cofactors include heme, iron-sulfur clusters, and simple iron ions. Poly(rC)-binding proteins are multifunctional adaptors that serve as iron ion chaperones in the cytosolic/nuclear compartment, binding iron at import and delivering it to enzymes, for storage (ferritin), and export (ferroportin). Ferritin iron is mobilized by autophagy through the cargo receptor, nuclear co-activator 4...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28615197/microtubule-regulation-and-function-during-virus-infection
#12
Mojgan H Naghavi, Derek Walsh
Microtubules (MTs) form a rapidly adaptable network of filaments that radiate throughout the cell. These dynamic arrays facilitate a wide range of cellular processes including the capture, transport and spatial organization of cargos and organelles, as well as changes in cell shape, polarity and motility. Nucleating from MT organizing centers including, but by no means limited to the centrosome, MTs undergo rapid transitions through phases of growth, pause and catastrophe, continuously exploring and adapting to the intracellular environment...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28607529/ev-associated-mmp9-in-high-grade-serous-ovarian-cancer-is-preferentially-localized-to-annexin-v-binding-evs
#13
Agnes T Reiner, Sisareuth Tan, Christiane Agreiter, Katharina Auer, Anna Bachmayr-Heyda, Stefanie Aust, Nina Pecha, Mattias Mandorfer, Dietmar Pils, Alain R Brisson, Robert Zeillinger, Sai Kiang Lim
High-grade serous ovarian cancer (HGSOC) is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers. Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications. Hence, new biomarkers for HGSOC are urgently required. This study aimed to identify new markers by isolating different extracellular vesicle (EV) types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo...
2017: Disease Markers
https://www.readbyqxmd.com/read/28607115/surface-lamp-2-is-an-endocytic-receptor-that-diverts-antigen-internalized-by-human-dendritic-cells-into-highly-immunogenic-exosomes
#14
Dario Armando Leone, Andrea Peschel, Markus Brown, Helga Schachner, Miriam J Ball, Marianna Gyuraszova, Ulrike Salzer-Muhar, Minoru Fukuda, Caterina Vizzardelli, Barbara Bohle, Andrew J Rees, Renate Kain
The lysosome-associated membrane protein (LAMP) family includes the dendritic cell endocytic receptors DC-LAMP and CD68, as well as LAMP-1 and LAMP-2. In this study we identify LAMP-1 (CD107a) and LAMP-2 (CD107b) on the surface of human monocyte-derived dendritic cells (MoDC) and show only LAMP-2 is internalized after ligation by specific Abs, including H4B4, and traffics rapidly but transiently to the MHC class II loading compartment, as does Ag conjugated to H4B4. However, pulsing MoDC with conjugates of primary (keyhole limpet hemocyanin; KLH) and recall (Bet v 1) Ags (H4B4*KLH and H4B4*Bet v 1) induced significantly less CD4 cell proliferation than pulsing with native Ag or Ag conjugated to control mAb (ISO*KLH and ISO*Bet v 1)...
June 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28603700/the-type-ix-secretion-system-t9ss-highlights-and-recent-insights-into-its-structure-and-function
#15
REVIEW
Anna M Lasica, Miroslaw Ksiazek, Mariusz Madej, Jan Potempa
Protein secretion systems are vital for prokaryotic life, as they enable bacteria to acquire nutrients, communicate with other species, defend against biological and chemical agents, and facilitate disease through the delivery of virulence factors. In this review, we will focus on the recently discovered type IX secretion system (T9SS), a complex translocon found only in some species of the Bacteroidetes phylum. T9SS plays two roles, depending on the lifestyle of the bacteria. It provides either a means of movement (called gliding motility) for peace-loving environmental bacteria or a weapon for pathogens...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28602352/cryo-em-reveals-how-human-cytoplasmic-dynein-is-auto-inhibited-and-activated
#16
Kai Zhang, Helen E Foster, Arnaud Rondelet, Samuel E Lacey, Nadia Bahi-Buisson, Alexander W Bird, Andrew P Carter
Cytoplasmic dynein-1 binds dynactin and cargo adaptor proteins to form a transport machine capable of long-distance processive movement along microtubules. However, it is unclear why dynein-1 moves poorly on its own or how it is activated by dynactin. Here, we present a cryoelectron microscopy structure of the complete 1.4-megadalton human dynein-1 complex in an inhibited state known as the phi-particle. We reveal the 3D structure of the cargo binding dynein tail and show how self-dimerization of the motor domains locks them in a conformation with low microtubule affinity...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28600323/rab7-palmitoylation-is-required-for-efficient-endosome-to-tgn-trafficking
#17
Graziana Modica, Olga Skorobogata, Etienne Sauvageau, Adriano Vissa, Christopher M Yip, Peter K Kim, Hugo Wurtele, Stephane Lefrancois
Retromer is a multimeric protein complex that mediates endosome-to-TGN and endosome-to-plasma membrane trafficking of integral membrane proteins. Dysfunction of this complex has been linked to Alzheimer's and Parkinson's disease. The recruitment of retromer to endosomes is regulated by Rab7 to coordinate endosome-to- TGN trafficking of cargo-receptor complexes. Rab7 is also required for the degradation of internalized integral membrane proteins such as the epidermal growth factor receptor. We found that Rab7 is palmitoylated and that this modification is not required for membrane anchoring...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28597544/endoplasmic-reticulum-proteins-sdf2-and-sdf2l1-act-as-components-of-the-bip-chaperone-cycle-to-prevent-protein-aggregation
#18
Tsutomu Fujimori, Ryoji Suno, Shun-Ichiro Iemura, Tohru Natsume, Ikuo Wada, Nobuko Hosokawa
The folding of newly synthesized proteins in the endoplasmic reticulum (ER) is assisted by ER-resident chaperone proteins. BiP (immunoglobulin heavy-chain-binding protein), a member of the HSP70 family, plays a central role in protein quality control. The chaperone function of BiP is regulated by its intrinsic ATPase activity, which is stimulated by ER-resident proteins of the HSP40/DnaJ family, including ERdj3. Here, we report that two closely related proteins, SDF2 and SDF2L1, regulate the BiP chaperone cycle...
June 9, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28596424/s100-a9-protein-in-exosomes-from-chronic-lymphocytic-leukemia-cells-promotes-nf-%C3%AE%C2%BAb-activity-during-disease-progression
#19
Daniel Prieto, Natalia Sotelo, Noé Seija, Sandra Sernbo, Cecilia Abreu, Rosario Durán, Magdalena Gil, Estefanía Sicco, Victoria Irigoin, Carolina Oliver, Ana Inés Landoni, Raúl Gabus, Guillermo Dighiero, Pablo Oppezzo
Chronic Lymphocytic Leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. A continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of the exosomes are altered as tumors progress to an aggressive phenotype...
June 8, 2017: Blood
https://www.readbyqxmd.com/read/28595321/mitochondrial-deficits-and-abnormal-mitochondrial-retrograde-axonal-transport-play-a-role-in-the-pathogenesis-of-mutant-hsp27-induced-charcot-marie-tooth-disease
#20
Bernadett Kalmar, Amy Innes, Klaus Wanisch, Alicia Koyen Kolaszynska, Amelie Pandraud, Gavin Kelly, Andrey Y Abramov, Mary M Reilly, Giampietro Schiavo, Linda Greensmith
Mutations in the small heat shock protein Hsp27, encoded by the HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits have been implicated in the disease. In this study, we conducted analysis of bidirectional movements of mitochondria in primary motor neuron axons expressing wild type and mutant Hsp27. We found significantly slower retrograde transport of mitochondria in Ser135Phe, Pro39Leu and Arg140Gly mutant Hsp27 expressing motor neurons than in wild type Hsp27 neurons, although anterograde movement velocities remained normal...
June 8, 2017: Human Molecular Genetics
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