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clathrin endocytosis

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https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#1
Hideki Yamamoto, Daisuke Umeda, Shinji Matsumoto, Akira Kikuchi
Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a coreceptor of the Wnt signaling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane-a process known as transcytosis. Herein, we show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL...
August 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28821057/a-cell-penetrating-peptide-mediated-chitosan-nanocarriers-for-improving-intestinal-insulin-delivery
#2
Lei Li, Liaoqing Yang, Manman Li, Liefeng Zhang
To overcome barriers for oral delivery of insulin, the chitosan(CS)-based nanocarriers with a novel cell penetrating peptide (SAR6EW) have been prepared and evaluated in this study. Characterization measurements showed that SAR6EW/CS/insulin-NPs displayed global particles with smooth surfaces and an average diameter about 150nm. The entrapment efficiency and loading rates of insulin were 75.36% and 7.58%, respectively. Insulin could be released constantly from SAR6EW/CS/insulin-NPs in vitro. Furthermore, SAR6EW/CS/insulin-NPs could facilitate the uptake of insulin and induce a significantly higher internalization of insulin via adding clathrin and caveolae mediated endocytosis...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28821028/targeted-gene-delivery-of-polyethyleneimine-grafted-chitosan-with-rgd-dendrimer-peptide-in-%C3%AE-v%C3%AE-3-integrin-overexpressing-tumor-cells
#3
Young-Min Kim, Seong-Cheol Park, Mi-Kyeong Jang
The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful gene therapy has been limited. In the present study, a targeted gene carrier for αvβ3 integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated...
October 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28814867/exploring-cellular-uptake-of-iron-oxide-nanoparticles-associated-with-rhodium-citrate-in-breast-cancer-cells
#4
Natalia L Chaves, Irina Estrela-Lopis, Julia Böttner, Cláudio Ap Lopes, Bruna C Guido, Aparecido R de Sousa, Sônia N Báo
Nanocarriers have the potential to improve the therapeutic index of currently available drugs by improving their efficacy and achieving therapeutic steady-state levels over an extended period. The association of maghemite-rhodium citrate (MRC) nanoparticles (NPs) has the potential to increase specificity of the cytotoxic action. However, the interaction of these NPs with cells, their uptake mechanism, and subcellular localization need to be elucidated. This work evaluates the uptake mechanism of MRC NPs in metastatic and nonmetastatic breast cancer-cell models, comparing them to a nontumor cell line...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28814834/intracellular-trafficking-of-new-anticancer-therapeutics-antibody-drug-conjugates
#5
REVIEW
Muhammad Kalim, Jie Chen, Shenghao Wang, Caiyao Lin, Saif Ullah, Keying Liang, Qian Ding, Shuqing Chen, Jinbiao Zhan
Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28814502/selective-regulation-of-clathrin-mediated-egfr-signaling-and-endocytosis-by-phospholipase-c-and-calcium
#6
Ralph Christian Delos Santos, Stephen Bautista, Stefanie Lucarelli, Leslie N Bone, Roya M Dayam, John Abousawan, Roberto J Botelho, Costin N Antonescu
Clathrin-mediated endocytosis is a major regulator of cell surface protein internalization. Clathrin and other proteins assemble into small invaginating structures at the plasma membrane termed clathrin-coated pits (CCPs) that mediate vesicle formation. In addition, epidermal growth factor (EGF) receptor (EGFR) signaling is regulated by its accumulation within CCPs. Given the diversity of proteins regulated by clathrin-mediated endocytosis, how this process may distinctly regulate specific receptors is a key question...
August 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28813441/cross-over-endocytosis-of-claudins-is-mediated-by-interactions-via-their-extracellular-loops
#7
Nora Gehne, Agathe Lamik, Martin Lehmann, Reiner F Haseloff, Anuska V Andjelkovic, Ingolf E Blasig
Claudins (Cldns) are transmembrane tight junction (TJ) proteins that paracellularly seal endo- and epithelial barriers by their interactions within the TJs. However, the mechanisms allowing TJ remodeling while maintaining barrier integrity are largely unknown. Cldns and occludin are heterophilically and homophilically cross-over endocytosed into neighboring cells in large, double membrane vesicles. Super-resolution microscopy confirmed the presence of Cldns in these vesicles and revealed a distinct separation of Cldns derived from opposing cells within cross-over endocytosed vesicles...
2017: PloS One
https://www.readbyqxmd.com/read/28808055/dynamin-dependent-amino-acid-endocytosis-activates-mechanistic-target-of-rapamycin-complex-1-mtorc1
#8
Shusaku Shibutani, Hana Okazaki, Hiroyuki Iwata
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb)...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28799243/escherichia-coli-k1-utilises-host-macropinocytic-pathways-for-invasion-of-brain-microvascular-endothelial-cells
#9
Lip Nam Loh, Elizabeth M C McCarthy, Priyanka Narang, Naveed A Khan, Theresa H Ward
Eukaryotic cells utilise multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood-brain barrier, but the entry route remains unclear. Here we demonstrate that the bacteria trigger an actin-mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion...
August 11, 2017: Traffic
https://www.readbyqxmd.com/read/28796282/disulfide-bond-containing-agamatine-cystaminebisacrylamide-polymer-demonstrates-better-transfection-efficiency-and-lower-cytotoxicity-than-polyethylenimine-in-nih-3t3-cells
#10
Zhen Yang, Yanping Sun, Lei Xian, Zhe Xun, Jiankun Yu, Tianzhi Yang, Xiaoyun Zhao, Cuifang Cai, Dongkai Wang, Pingtian Ding
Previously, we synthesized a non-viral vector containing disulfide bond by polymerization of agamatine (AGM) and N, N'-cystaminebisacrylamide (CBA). In this study, we investigated the transfection efficiency of disulfide bond (-SS-) containing AGM-CBA polymer in gene delivery into NIH/3T3 cells, and examined the factors affecting its transfection efficiency by comparing with polyethylenimine (PEI). In addition, experiments were carried out to determine the mechanisms of cell entry pathways and intracellular behavior of AGM-CBA/pDNA polyplexes...
August 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28795274/novel-gemcitabine-conjugated-albumin-nanoparticles-a-potential-strategy-to-enhance-drug-efficacy-in-pancreatic-cancer-treatment
#11
Varun Kushwah, Ashish Kumar Agrawal, Chander Parkash Dora, David Mallinson, Dimitrios A Lamprou, Ramesh C Gupta, Sanyog Jain
PURPOSE: The present study reports a novel conjugate of gemcitabine (GEM) with bovine serum albumin (BSA) and thereof nanoparticles (GEM-BSA NPs) to potentiate the therapeutic efficacy by altering physicochemical properties, improving cellular uptake and stability of GEM. METHODS: The synthesized GEM-BSA conjugate was extensively characterized by NMR, FTIR, MALDI-TOF and elemental analysis. Conjugation mediated changes in structural conformation and physicochemical properties were analysed by fluorescence, Raman and CD spectroscopy, DSC and contact angle analysis...
August 9, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28791645/measurement-of-epidermal-growth-factor-receptor-derived-signals-within-plasma-membrane-clathrin-structures
#12
Stefanie Lucarelli, Ralph Christian Delos Santos, Costin N Antonescu
The epidermal growth factor (EGF) receptor (EGFR) is an important regulator of cell growth, proliferation, survival, migration, and metabolism. EGF binding to EGFR triggers the activation of the receptor's intrinsic kinase activity, in turn eliciting the recruitment of many secondary signaling proteins and activation of downstream signals, such as the activation of phosphatidylinositol-3-kinase (PI3K) and Akt, a process requiring the phosphorylation of Gab1. While the identity of many signals that can be activated by EGFR has been revealed, how the spatiotemporal organization of EGFR signaling within cells controls receptor outcome remains poorly understood...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28777555/effect-of-molecular-architecture-on-cell-interactions-and-stealth-properties-of-peg
#13
Imran Ozer, Aysel Tomak, Hadi M Zareie, Yusuf Baran, Volga Bulmus
PEGylation, covalent attachment of PEG to therapeutic biomolecules, in which sub-optimal pharmacokinetic profiles limiting their therapeutic utility are of concern, is a widely applied technology. However, this technology has been challenged by reduced bioactivity and biorecognition ability of biomolecules upon PEGylation and immunogenicity of PEG triggering immune response and abrogating clinical efficacy, which collectively necessitate development of stealth polymer alternatives. In this study, poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA), increasingly used as a stealth polymer alternative, has been compared with PEG counterpart in terms of physicochemical properties, in vitro cell interaction profiles and steric hindrance imposed on the conjugated biomolecules...
August 4, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28776948/precise-labelling-and-tracking-lipid-droplet-in-adipocytes-using-a-luminescent-znsalen-complex
#14
Juan Tang, Yanfei Zhang, Hao-Yan Yin, Guoheng Xu, Jun-Long Zhang
Designing two-photon probes for precise labelling lipid droplet (LD) and monitoring LD dynamics in adipocytes is of great significance to understand LD homeostasis. We herein report that a luminescent metal complex LD-TPZn can specifically image LDs in adipose cells and tissue using one- or two-photon fluorescence microscopy. Importantly, LD-TPZn exhibited higher specificity to LD than commercial Nile Red and Bodipy 493/503, probably due to different cellular uptake pathways, clathrin-mediated endocytosis and non-selectively passive diffusion, respectively...
August 4, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28770233/airway-epithelial-repair-by-a-prebiotic-mannan-derived-from-saccharomyces-cerevisiae
#15
Christie F Michael, Christopher M Waters, Kim S LeMessurier, Amali E Samarasinghe, Chi Y Song, Kafait U Malik, D Betty Lew
In asthmatic airways, repeated epithelial damage and repair occur. No current therapy directly targets this process. We aimed to determine the effects of mannan derived from S. cerevisiae (SC-MN) on airway epithelial wound repair, in vitro. The presence of functional mannose receptors in bronchial epithelial cells was shown by endocytosis of colloidal gold-Man BSA via clathrin-coated pits in 16HBE cells. In primary normal human bronchial epithelial cells (NHBEC), SC-MN significantly facilitated wound closure...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28769563/delivery-of-mir-375-and-doxorubicin-hydrochloride-by-lipid-coated-hollow-mesoporous-silica-nanoparticles-to-overcome-multiple-drug-resistance-in-hepatocellular-carcinoma
#16
Huiying Xue, Zhaoyang Yu, Yong Liu, Weigang Yuan, Tan Yang, Jia You, Xingxing He, Robert J Lee, Lei Li, Chuanrui Xu
Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that miR-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and miR-375 (LHD/miR-375) to deliver the two agents into MDR HCC cells in vitro and in vivo...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28769084/antibody-induced-dimerization-of-fgfr1-promotes-receptor-endocytosis-independently-of-its-kinase-activity
#17
Łukasz Opaliński, Aleksandra Sokołowska-Wędzina, Martyna Szczepara, Małgorzata Zakrzewska, Jacek Otlewski
Fibroblast growth factors (FGFs) and their plasma membrane-localized receptors (FGFRs) play a key role in the regulation of developmental processes and metabolism. Aberrant FGFR signaling is associated with the progression of serious metabolic diseases and human cancer. Binding of FGFs to FGFRs induces receptor dimerization and transphosphorylation of FGFR kinase domains that triggers activation of intracellular signaling pathways. Following activation, FGFRs undergo internalization and subsequent lysosomal degradation, which terminates transmission of signals...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761339/systemic-delivery-of-the-anticancer-agent-arenobufagin-using-polymeric-nanomicelles
#18
Xue Yuan, Qian Xie, Keyu Su, Zhijie Li, Dong Dong, Baojian Wu
Arenobufagin (ABG) is a major active component of toad venom, a traditional Chinese medicine used for cancer therapy. However, poor aqueous solubility limits its pharmacological studies in vivo due to administration difficulties. In this study, we aimed to develop a polymeric nanomicelle (PN) system to enhance the solubility of ABG for effective intravenous delivery. ABG-loaded PNs (ABG-PNs) were prepared with methoxy poly (ethylene glycol)-block-poly (d,l-lactic-co-glycolic acid) (mPEG-PLGA) using the solvent-diffusion technique...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28761175/rock1-is-a-novel-rac1-effector-to-regulate-tubular-endocytic-membrane-formation-during-clathrin-independent-endocytosis
#19
David Soriano-Castell, Albert Chavero, Carles Rentero, Marta Bosch, Maite Vidal-Quadras, Albert Pol, Carlos Enrich, Francesc Tebar
Clathrin-dependent and -independent pathways contribute for β1-integrin endocytosis. This study defines a tubular membrane clathrin-independent endocytic network, induced with the calmodulin inhibitor W13, for β1-integrin internalization. This pathway is dependent on increased phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels and dynamin activity at the plasma membrane. Exogenous addition of PI(4,5)P2 or phosphatidylinositol-4-phosphate 5-kinase (PIP5K) expression mimicked W13-generated-tubules which are inhibited by active Rac1...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761128/blockade-of-dengue-virus-infection-and-viral-cytotoxicity-in-neuronal-cells-in-vitro-and-in-vivo-by-targeting-endocytic-pathways
#20
Min-Ru Ho, Tsung-Ting Tsai, Chia-Ling Chen, Ming-Kai Jhan, Cheng-Chieh Tsai, Yi-Chao Lee, Chun-Han Chen, Chiou-Feng Lin
Dengue virus (DENV) infection in neuronal cells was speculated to trigger neuropathy. Herein, we determined the blockade of DENV infection by targeting endocytic pathways in vitro and in vivo. In DENV-infected mouse brains, we previously showed that viral proteins are expressed in neuronal cells around the hippocampus with accompanying neurotoxicity. DENV caused infection, including entry, double-stranded (ds)RNA replication, protein expression, and virus release, followed by cytotoxicity in the mouse neuronal Neuro-2a cell line...
July 31, 2017: Scientific Reports
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