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Endocytosis

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https://www.readbyqxmd.com/read/29057905/albumin-uptake-in-human-podocytes-a-possible-role-for-the-cubilin-amnionless-cubam-complex
#1
Lisa Gianesello, Giovanna Priante, Monica Ceol, Claudia M Radu, Moin A Saleem, Paolo Simioni, Liliana Terrin, Franca Anglani, Dorella Del Prete
Albumin re-uptake is a receptor-mediated pathway located in renal proximal tubuli. There is increasing evidence of glomerular protein handling by podocytes, but little is known about the mechanism behind this process. In this study, we found that human podocytes in vitro are committed to internalizing albumin through a receptor-mediated mechanism even after exposure to low doses of albumin. We show that these cells express cubilin, megalin, ClC-5, amnionless and Dab2, which are partners in the tubular machinery...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29056306/imaging-in-focus-imaging-the-dynamics-of-endocytosis
#2
Morgane Rosendale, David Perrais
Endocytosis, the formation of membrane vesicles from the plasma membrane, is an essential feature of eukaryotic cell biology. Intense research effort has been dedicated to developing methods that can detect endocytosis events with the highest resolution. We have classified these methods into four families. They exploit the physical properties of endocytosis, namely: 1. Distinguishing extracellular from internalised cargo in fixed samples, 2. Monitoring endosomal acidification, 3. Measuring the turnover of endocytic zones and 4...
October 19, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29056027/-differential-expression-of-micrornas-in-serum-of-severe-burn-patients-and-analysis-of-the-signaling-pathway-at-early-stage
#3
S Wang, Q F Ruan, W G Xie, L Chen, M J Jiang, J J Ruan, Z Q Ye
Objective: To explore differential expression of microRNAs in serum of patients with severe burn and analysis of the signaling pathway at early stage. Methods: In this study, we included three healthy adult volunteers and three patients with severe burn, conforming to the inclusion criteria and hospitalized in Tongren Hospital of Wuhan University & Wuhan Third Hospital in July 2015. Venous whole blood of 6 mL of each burn patient and healthy volunteer was collected at 24 to 48 h post injury of burn patients...
October 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/29055774/functional-nanoparticles-exploit-the-bile-acid-pathway-to-overcome-multiple-barriers-of-the-intestinal-epithelium-for-oral-insulin-delivery
#4
Weiwei Fan, Dengning Xia, Quanlei Zhu, Xiuying Li, Shufang He, Chunliu Zhu, Shiyan Guo, Lars Hovgaard, Mingshi Yang, Yong Gan
Oral absorption of protein/peptide-loaded nanoparticles is often limited by multiple barriers of the intestinal epithelium. In addition to mucus translocation and apical endocytosis, highly efficient transepithelial absorption of nanoparticles requires successful intracellular trafficking, especially to avoid lysosomal degradation, and basolateral release. Here, the functional material, deoxycholic acid-conjugated chitosan, is synthesized and loaded with the model protein drug insulin into deoxycholic acid-modified nanoparticles (DNPs)...
October 13, 2017: Biomaterials
https://www.readbyqxmd.com/read/29054985/caveolae-mediated-endocytosis-as-a-novel-mechanism-of-resistance-to-trastuzumab-emtansine-t-dm1
#5
Matthew Sung, Xingzhi Tan, Bingwen Lu, Jonathan Golas, Christine Hosselet, Fang Wang, Laurie Tylaska, Lindsay King, Dahui Zhou, Russell Dushin, Jeremy S Myers, Edward Rosfjord, Judy Lucas, Hans-Peter Gerber, Frank Loganzo
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that has demonstrated clinical benefit for patients with HER2+ metastatic breast cancer, however its clinical activity is limited by inherent or acquired drug resistance. The molecular mechanisms that drive clinical resistance to T-DM1, especially in HER2+ tumors, are not well understood. We used HER2+ cell lines to develop models of T-DM1 resistance utilizing a cyclical dosing schema in which cells received T-DM1 in an "on-off" routine until a T-DM1 resistant population was generated...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29054930/the-transcription-factor-mef2a-fine-tunes-gene-expression-in-the-atrial-and-ventricular-chambers-of-the-adult-heart
#6
Jose L Medrano, Francisco J Naya
The distinct morphological and functional properties of the cardiac chambers arise from an elaborate developmental program involving cell lineage determination, morphogenesis, and dynamic spatiotemporal gene expression patterns. While a number of transcription factors have been identified for proper gene regulation in the chambers, the complete transcriptional network that controls these patterns remains poorly defined. Previous studies have implicated the MEF2C transcription factor in the regulation of chamber-restricted enhancers...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29054882/parkinson-s-disease-associated-lrrk2-hyperactive-kinase-mutant-disrupts-synaptic-vesicle-trafficking-in-ventral-midbrain-neurons
#7
Ping-Yue Pan, Xianting Li, Jing Wang, James Powell, Qian Wang, Yuanxi Zhang, Zhaoyu Chen, Bridget Wicinski, Patrick Hof, Timothy A Ryan, Zhenyu Yue
Parkinson's disease (PD) is characterized pathologically by the selective loss of substantia nigra (SN) dopaminergic (DAergic) neurons. Recent evidence has suggested a role of LRRK2, linked to the most frequent familial PD, in regulating synaptic vesicle (SV) trafficking. However, the mechanism whereby LRRK2 mutants contribute to nigral vulnerability remains unclear. Here we show that the most common PD mutation LRRK2 G2019S impairs SV endocytosis in ventral midbrain (MB) neurons including DA neurons, and the slowed endocytosis can be rescued by inhibition of LRRK2 kinase activity...
October 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29054428/%C3%AE-arrestin2-directly-or-through-grk2-inhibits-pkc%C3%AE-ii-activation-in-a-ubiquitination-dependent-manner
#8
Xiaohan Zhang, Mei Zheng, Ningning Sun, Kyeong-Man Kim
The GRK/β-arrestin and PKC/PKA mediate the homologous and heterologous regulation of G protein-coupled receptors (GPCRs), respectively. Interaction between the two pathways is one of the most important issues in understanding the regulation of GPCRs. The present study investigated the regulatory effect of GRK2 and β-arrestins on PKC activation. The roles of GRK2 and β-arrestins in the functional regulation of PKC were assessed by determining their influence on PKC autophosphorylation and intracellular translocation...
October 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29054027/sapofectosid-ensuring-non-toxic-and-effective-dna-and-rna-delivery
#9
Simko Sama, Gerold Jerz, Peter Schmieder, Eric Woith, Matthias F Melzig, Alexander Weng
Different methods are being deployed for non-viral DNA/RNA delivery. However non-viral formulations for DNA/RNA-delivery are often accompanied by severe toxicity and thus low efficiency. Particular costly cell culture media are required as well. Here we introduce sapofection as a valuable enhancing method for non-viral DNA/RNA delivery. Sapofection is based on the application of DNA/RNA nanoplexes and sapofectosid, a plant derived natural transfection reagent. Sapofectosid was produced from plant raw material by chromatographic methods and characterized by tandem mass spectrometry and intensive one and two dimensional NMR-spectroscopy...
October 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29053588/yeast-killer-toxin-k28-biology-and-unique-strategy-of-host-cell-intoxication-and-killing
#10
REVIEW
Björn Becker, Manfred J Schmitt
The initial discovery of killer toxin-secreting brewery strains of Saccharomyces cerevisiae (S. cerevisiae) in the mid-sixties of the last century marked the beginning of intensive research in the yeast virology field. So far, four different S. cerevisiae killer toxins (K28, K1, K2, and Klus), encoded by cytoplasmic inherited double-stranded RNA viruses (dsRNA) of the Totiviridae family, have been identified. Among these, K28 represents the unique example of a yeast viral killer toxin that enters a sensitive cell by receptor-mediated endocytosis to reach its intracellular target(s)...
October 20, 2017: Toxins
https://www.readbyqxmd.com/read/29053471/pegylated-anticancer-carbon-nanotubes-complex-targeting-mitochondria-of-lung-cancer-cells
#11
Sang-Woo Kim, Yeon Kyung Lee, Jong Yeon Lee, Jeong Hee Hong, Dongwoo Khang
Although activating apoptosis in cancer cells by targeting the mitochondria is an effective strategy for cancer therapy, insufficient targeting of the mitochondria in cancer cells restricts the availability in clinical treatment. Here, we report on a polyethylene glycol-coated carbon nanotube (CNT)-ABT737 nanodrug that improves the mitochondrial targeting of lung cancer cells. The polyethylene glycol-coated CNT-ABT737 nanodrug internalized into the early endosomes via macropinocytosis and clathrin-mediated endocytosis in advance of early endosomal escape and delivered into the mitochondria...
October 20, 2017: Nanotechnology
https://www.readbyqxmd.com/read/29051140/fgd5-faciogenital-dysplasia-5-regulates-vegf-vascular-endothelial-growth-factor-a-receptor-2-coupling-to-pi3-phosphoinositide-3-kinase-and-receptor-recycling
#12
Maikel A Farhan, Abul K Azad, Nicolas Touret, Allan G Murray
OBJECTIVE: VEGF (vascular endothelial growth factor-A) signaling to the endothelial cell (EC) through VEGFR2 (VEGF receptor-2) is the principal cue driving new blood vessel formation. FGD5 (faciogenital dysplasia-5)-a Rho-family guanine nucleotide exchange factor-is selectively expressed in EC. Deficiency of FGD5 is embryonically lethal in mice and perturbs angiogenesis and VEGF signal transduction. However, the mechanism of FGD5 regulation of VEGF signaling is poorly understood. APPROACH AND RESULTS: Angiogenic sprouting and EC cytoskeletal remodeling were evaluated in a 3-dimensional (3D) in vitro model...
October 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29050600/evaluation-of-disulfide-bond-conjugated-lmwsc-g-bpei-as-non-viral-vector-for-low-cytotoxicity-and-efficient-gene-delivery
#13
Gyeong-Won Jeong, Jae-Woon Nah
For efficient gene delivery, non-viral vectors should have high cellular uptake, excellent endosomal escape, and the ability to rapidly release the gene into the cytoplasm. Here, we developed a disulfide bond-conjugated bioreducible LMWSC-g-bPEI (LCP) composed of low molecular-weight water soluble chitosan (LMWSC), bPEI, and cystamine (Cys). The developed LCP had advantages such as low toxicity, great endosomal escape, and rapid release of pDNA into the cytoplasm. The polyplexes with LCP showed higher uptake into the nucleus and greater transfection efficiency than that without disulfide bond...
December 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29048561/a-ca2-dependent-remodelled-actin-network-directs-vesicle-trafficking-to-build-wall-ingrowth-papillae-in-transfer-cells
#14
Hui-Ming Zhang, Kim Colyvas, John W Patrick, Christina E Offler, Simon Turner
The transport function of transfer cells is conferred by an enlarged plasma membrane area, enriched in nutrient transporters, that is supported on a scaffold of wall ingrowth (WI) papillae. Polarized plumes of elevated cytosolic Ca2+ define loci at which WI papillae form in developing adaxial epidermal transfer cells of Vicia faba cotyledons that are induced to trans-differentiate when the cotyledons are placed on culture medium. We evaluated the hypothesis that vesicle trafficking along a Ca2+-regulated remodelled actin network is the mechanism that underpins this outcome...
October 13, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29047044/exosomes-for-the-enhanced-tissue-bioavailability-and-efficacy-of-curcumin
#15
Farrukh Aqil, Radha Munagala, Jeyaprakash Jeyabalan, Ashish Kumar Agrawal, Ramesh Gupta
Exosomes are extracellular microvesicles with a particle size of 30-100 nm and carry a cargo of proteins, lipids, RNA, and DNA. Their properties of shuttling in-and-out of the cells suggest that these particles can be exploited as a nano drug carrier. In this manuscript, we show that curcumin can be delivered effectively using milk-derived exosomes. Curcumin when mixed with exosomes in the presence of 10% ethanol:acetonitrile (1:1) provided a drug load of 18-24%, and the formulation stored at - 80°C was stable for 6 months as determined by particle size analysis, drug load, and antiproliferative activity...
October 18, 2017: AAPS Journal
https://www.readbyqxmd.com/read/29046458/a-tyrosine-based-trafficking-motif-of-the-tegument-protein-pul71-is-crucial-for-human-cytomegalovirus-secondary-envelopment
#16
Andrea N Dietz, Clarissa Villinger, Stefan Becker, Manfred Frick, Jens von Einem
The human cytomegalovirus (HCMV) tegument protein pUL71 is required for efficient secondary envelopment and accumulates at the Golgi-derived viral assembly complex (vAC) during infection. Analysis of various C-terminally truncated pUL71 fused to eGFP identified amino acids 23-34 as important determinants for its Golgi localization. Sequence analysis and mutational verification revealed the presence of an N-terminal tyrosine-based trafficking motif (YxxΦ) in pUL71. This led us to hypothesize a requirement of the YxxΦ motif for the function of pUL71 in infection...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046140/amplification-of-arsenic-genotoxicity-by-tio2-nanoparticles-in-mammalian-cells-new-insights-from-physicochemical-interactions-and-mitochondria
#17
Xinan Wang, Yun Liu, Juan Wang, Yaguang Nie, Shaopeng Chen, Tom K Hei, Zhaoxiang Deng, Lijun Wu, Guoping Zhao, An Xu
Titanium dioxide nanoparticles (TiO2 NPs) have shown great adsorption capacity for arsenic (As); however, the potential impact of TiO2 NPs on the behavior and toxic responses of As remains largely unexplored. In the present study, we focused on the physicochemical interaction between TiO2 NPs and As(III) to clarify the underlying mechanisms involved in their synergistic genotoxic effect on mammalian cells. Our data showed that As(III) mainly interacted with TiO2 NPs by competitively occupying the sites of hydroxyl groups on the surface of TiO2 NP aggregates, resulting in more aggregation of TiO2 NPs...
October 18, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/29045873/nanoscale-membrane-budding-induced-by-ctxb-and-detected-via-polarized-localization-microscopy
#18
Abir M Kabbani, Christopher V Kelly
For endocytosis and exocytosis, membranes transition among planar, budding, and vesicular topographies through nanoscale reorganization of lipids, proteins, and carbohydrates. However, prior attempts to understand the initial stages of nanoscale bending have been limited by experimental resolution. Through the implementation of polarized localization microscopy, this article reports the inherent membrane bending capability of cholera toxin subunit B (CTxB) in quasi-one-component-supported lipid bilayers. Membrane buds were first detected with <50 nm radius, grew to >200 nm radius, and extended into longer tubules with dependence on the membrane tension and CTxB concentration...
October 17, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29044433/pregnancy-induced-changes-in-metabolome-and-proteome-in-ovine-uterine-flushings
#19
Jared J Romero, Bethany E Liebig, Corey D Broeckling, Jessica E Prenni, Thomas R Hansen
Mass spectrometry (MS) approaches were used herein to identify metabolites and proteins in uterine flushings (UF) that may contribute to nourishing the conceptus. Ovine uteri collected on Day 12 of the estrous cycle (n = 5 ewes exposed to vasectomized ram) or Days 12 (n = 4), 14 (n = 5), or 16 (n = 5) of pregnancy (bred with fertile ram) were flushed using buffered saline. Metabolites were extracted using 80% methanol and profiled using ultraperformance liquid chromatography (LC) tandem mass spectrometry. The proteome was examined by digestion with trypsin, followed by the analysis of peptides with LC-MS/MS...
August 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29044181/a-novel-%C3%AE-adaptin-c-myc-complex-formation-modulated-by-oxidative-stress-in-the-control-of-the-cell-cycle-in-macrophages-and-its-implication-in-atherogenesis
#20
Victor García-González, Jaime Mas-Oliva
Our study tested the proposal that c-Myc activation in macrophages is differentially carried out dependent on the intracellular oxidative state of cells and potentially associated to the process of atherogenesis. Under our experimental conditions, the generation of reactive oxygen species carried out by the presence of oxidized low density lipoproteins (oxLDL) or Gram negative bacterial lipopolysaccharides (LPS) modifies the expression of cellular adhesion molecules such as c-Abl, calcium transport proteins such as the plasma membrane Ca(2+)-ATPase (PMCA), CD47, procaspase-7, CASP7, CHOP, transcriptional activators such as c-Jun and c-Myc and molecules that participate in the process of endocytosis like α- and β-adaptin...
October 18, 2017: Scientific Reports
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