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Macropinocytosis

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https://www.readbyqxmd.com/read/28526602/palmitoyl-ascorbate-and-doxorubicin-co-encapsulated-liposome-for-synergistic-anticancer-therapy
#1
Yue Yang, Xiaoyu Lu, Qi Liu, Yu Dai, Xiaojie Zhu, Yanli Wen, Jiaqiu Xu, Yang Lu, Di Zhao, Xijing Chen, Ning Li
Combination therapy with two drugs and nanoparticle-based drug delivery systems are widely applied to reduce the adverse effects of traditional treatment by chemotherapeutic drugs. Palmitoyl ascorbate (PA) as a lipophilic derivative of ascorbic acid shows the advantages in cancer treatment. The aim of the study was to prepare a doxorubicin (DOX) and PA co-loaded liposome to synergistically treat tumor and effectively alleviate the toxicity caused by DOX. The effects were evaluated by in vitro and in vivo studies...
May 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28524754/arf-gtpase-interplay-with-rho-gtpases-in-regulation-of-the-actin-cytoskeleton
#2
Vikash Singh, Anthony C Davidson, Peter J Hume, Daniel Humphreys, Vassilis Koronakis
The Arf and Rho subfamilies of small GTPases are nucleotide-dependent molecular switches that act as master regulators of vesicular trafficking and the actin cytoskeleton organization. Small GTPases control cell processes with high fidelity by acting through distinct repertoires of binding partners called effectors. While we understand a great deal about how these GTPases act individually, relatively little is known about how they cooperate, especially in the control of effectors. This review highlights how Arf GTPases collaborate with Rac1 to regulate actin cytoskeleton dynamics at the membrane via recruiting and activating the Wave Regulatory Complex (WRC), a Rho effector that underpins lamellipodia formation and macropinocytosis...
May 19, 2017: Small GTPases
https://www.readbyqxmd.com/read/28522588/a-potential-mechanism-for-adc-induced-neutropenia-role-of-neutrophils-in-their-own-demise
#3
Hui Zhao, Sara Gulesserian, Maria Christina Malinao, Sathish Kumar-Ganesan, James Song, Mi Sook Chang, Melissa M Williams, Zhilan Zeng, Michael Mattie, Brian A Mendelsohn, David R Stover, Fernando Doñate
Neutropenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADCs) and we aimed to elucidate the potential mechanism of this toxicity. To investigate if ADCs affect neutrophil production from bone marrow, an in vitro assay was developed in which hematopoietic stem cells (HSCs) were differentiated to neutrophils. Several antibodies against targets absent in HSCs and neutrophils were conjugated to MMAE via a cleavable valine-citrulline linker (vcMMAE-ADCs) or MMAF via a non-cleavable maleimidocaproyl linker (mcMMAF-ADCs), and their cytotoxicity was tested in the neutrophil differentiation assay...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522322/imaging-macropinosomes-during-shigella-infections
#4
REVIEW
Noelia Lopez-Montero, Yuen-Yan Chang, Anna Sartori-Rupp, Sonja Kühn, Jost Enninga
Macropinocytosis is the uptake of extracellular fluid within vesicles of varying size that takes place during numerous cellular processes in a large variety of cells. A growing number of pathogens, including viruses, parasites, and bacteria are known to induce macropinocytosis during their entry into targeted host cells. We have recently discovered that the human enteroinvasive, bacterial pathogen Shigella causes in situ macropinosome formation during its entry into epithelial cells. These infection-associated macropinosomes are not generated to ingest the bacteria, but are instead involved in Shigella's intracellular niche formation...
May 15, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28516118/quantitative-measurements-of-hiv-1-and-dextran-capture-by-human-monocyte-derived-dendritic-cells-mddcs
#5
Mickaël M Ménager, Dan R Littman
The aim of this protocol is to describe how to measure and quantify the amount of HIV-1 particles and dextran molecules internalized in human monocyte derived dendritic cells (MDDCs), using three different techniques: flow cytometry, quantitative PCR and confocal microscopy. BACKGROUND: This protocol was developed in order to assess the changes of HIV-1 internalization upon disruption of actin nucleation in human monocyte derived dendritic cells. Following a shRNA screen to identify genes important for HIV-1 transfer from dendritic cells to T cells, we observed that a disruption of actin nucleation leads to a switch from actin rich dendrites to blebs, due to an excess of actomyosin contraction...
November 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28515429/endocytic-uptake-of-monomeric-amyloid-%C3%AE-peptides-is-clathrin-and-dynamin-independent-and-results-in-selective-accumulation-of-a%C3%AE-1-42-compared-to-a%C3%AE-1-40
#6
Emelie Wesén, Gavin D M Jeffries, Maria Matson Dzebo, Elin K Esbjörner
Intraneuronal accumulation of amyloid-β (Aβ) peptides represent an early pathological feature in Alzheimer's disease. We have therefore utilized flow cytometry and confocal microscopy in combination with endocytosis inhibition to explore the internalisation efficiency and uptake mechanisms of Aβ(1-40) and Aβ(1-42) monomers in cultured SH-SY5Y cells. We find that both variants are constitutively internalised via endocytosis and that their uptake is proportional to cellular endocytic rate. Moreover, SH-SY5Y cells internalise consistently twice the amount of Aβ(1-42) compared to Aβ(1-40); an imaging-based quantification showed that cells treated with 1 µM peptide for 8 h contained 800,000 peptides of Aβ(1-42) and 400,000 of Aβ(1-40)...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28512335/arginine-rich-cell-penetrating-peptide-modified-extracellular-vesicles-for-active-macropinocytosis-induction-and-efficient-intracellular-delivery
#7
Ikuhiko Nakase, Kosuke Noguchi, Ayako Aoki, Tomoka Takatani-Nakase, Ikuo Fujii, Shiroh Futaki
Extracellular vesicles (EVs) including exosomes have been shown to play crucial roles in cell-to-cell communication because of their ability to carry biofunctional molecules (e.g., microRNAs and enzymes). EVs also have pharmaceutical advantages and are highly anticipated to be a next-generation intracellular delivery tool. Here, we demonstrate an experimental technique that uses arginine-rich cell-penetrating peptide (CPP)-modified EVs to induce active macropinocytosis for effective cellular EV uptake. Modification of arginine-rich CPPs on the EV membrane resulted in the activation of the macropinocytosis pathway, and the number of arginine residues in the peptide sequences affected the cellular EV uptake efficiency...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490792/length-effects-on-the-dynamic-process-of-cellular-uptake-and-exocytosis-of-single-walled-carbon-nanotubes-in-murine-macrophage-cells
#8
Xuejing Cui, Bin Wan, Yu Yang, Xiaomin Ren, Liang-Hong Guo
Cellular uptake and exocytosis of SWCNTs are fundamental processes determining their intracellular concentration and effects. Despite the great potential of acid-oxidized SWCNTs in biomedical field, understanding of the influencing factors on these processes needs to be deepened. Here, we quantitatively investigated uptake and exocytosis of SWCNTs in three lengths-630 (±171) nm (L-SWCNTs), 390 (±50) nm (M-SWCNTs), and 195 (±63) nm (S-MWCNTs) in macrophages. The results showed that the cellular accumulation of SWCNTs was a length-independent process and non-monotonic in time, with the most SWCNTs (3950 fg/cell) accumulated at 8 h and then intracellular SWCNTs dropped obviously with time...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28489075/lipoprotein-biomimetic-nanostructure-enables-efficient-targeting-delivery-of-sirna-to-ras-activated-glioblastoma-cells-via-macropinocytosis
#9
Jia-Lin Huang, Gan Jiang, Qing-Xiang Song, Xiao Gu, Meng Hu, Xiao-Lin Wang, Hua-Hua Song, Le-Pei Chen, Ying-Ying Lin, Di Jiang, Jun Chen, Jun-Feng Feng, Yong-Ming Qiu, Ji-Yao Jiang, Xin-Guo Jiang, Hong-Zhuan Chen, Xiao-Ling Gao
Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to 'drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma...
May 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28475901/snapshot-macropinocytosis
#10
Pedro E Marques, Sergio Grinstein, Spencer A Freeman
Macropinocytosis is the bulk ingestion of extracellular fluids via large endocytic vacuoles. This SnapShot provides an overview of physiological macropinocytosis in immune surveillance and its pathogenic contribution during infection and cancer proliferation.
May 4, 2017: Cell
https://www.readbyqxmd.com/read/28472637/lipid-oligonucleotide-conjugates-improve-cellular-uptake-and-efficiency-of-tctp-antisense-in-castration-resistant-prostate-cancer
#11
Sara Karaki, Sebastien Benizri, Raquel Mejías, Virginie Baylot, Nicolas Branger, Tan Nguyen, Brune Vialet, Khalid Oumzil, Philippe Barthélémy, Palma Rocchi
Translationally controlled tumor protein (TCTP) has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. Therefore, TCTP is now recognized as a potential therapeutic target in several cancers including prostate, breast and lung cancers. We previously showed that TCTP is overexpressed in castration-resistant prostate cancer (CRPC), and it has been implicated resistance to treatment. Recently, we developed TCTP antisense oligonucleotides (ASOs) to inhibit TCTP expression...
May 1, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28468978/regulation-of-circular-dorsal-ruffles-macropinocytosis-and-cell-migration-by-rhog-and-its-exchange-factor-trio
#12
Alejandra Valdivia, Silvia M Goicoechea, Sahezeel Awadia, Ashtyn Zinn, Rafael Garcia-Mata
Circular dorsal ruffles (CDRs) are actin-rich structures that form on the dorsal surface of many mammalian cells in response to growth factor stimulation. CDRs represent a unique type of structure that forms transiently and only once upon stimulation. The formation of CDRs involves a drastic rearrangement of the cytoskeleton, which is regulated by the Rho family of GTPases. So far, only Rac1 has been consistently associated with CDR formation, whereas the role of other GTPases in this process is either lacking or inconclusive...
May 3, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28467910/targeting-ras-driven-cancer-cell-survival-and-invasion-through-selective-inhibition-of-dock1
#13
Hirotada Tajiri, Takehito Uruno, Takahiro Shirai, Daisuke Takaya, Shigeki Matsunaga, Daiki Setoyama, Mayuki Watanabe, Mutsuko Kukimoto-Niino, Kounosuke Oisaki, Miho Ushijima, Fumiyuki Sanematsu, Teruki Honma, Takaho Terada, Eiji Oki, Senji Shirasawa, Yoshihiko Maehara, Dongchon Kang, Jean-François Côté, Shigeyuki Yokoyama, Motomu Kanai, Yoshinori Fukui
Oncogenic Ras plays a key role in cancer initiation but also contributes to malignant phenotypes by stimulating nutrient uptake and promoting invasive migration. Because these latter cellular responses require Rac-mediated remodeling of the actin cytoskeleton, we hypothesized that molecules involved in Rac activation may be valuable targets for cancer therapy. We report that genetic inactivation of the Rac-specific guanine nucleotide exchange factor DOCK1 ablates both macropinocytosis-dependent nutrient uptake and cellular invasion in Ras-transformed cells...
May 2, 2017: Cell Reports
https://www.readbyqxmd.com/read/28431576/enhanced-neuroinvasion-by-smaller-soluble-prions
#14
Cyrus Bett, Jessica Lawrence, Timothy D Kurt, Christina Orru, Patricia Aguilar-Calvo, Anthony E Kincaid, Witold K Surewicz, Byron Caughey, Chengbiao Wu, Christina J Sigurdson
Infectious prion aggregates can propagate from extraneural sites into the brain with remarkable efficiency, likely transported via peripheral nerves. Yet not all prions spread into the brain, and the physical properties of a prion that is capable of transit within neurons remain unclear. We hypothesized that small, diffusible aggregates spread into the CNS via peripheral nerves. Here we used a structurally diverse panel of prion strains to analyze how the prion conformation impacts transit into the brain. Two prion strains form fibrils visible ultrastructurally in the brain in situ, whereas three strains form diffuse, subfibrillar prion deposits and no visible fibrils...
April 21, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28431548/water-pipe-smoke-condensate-increases-the-internalization-of-mycobacterium-bovis-of-type-ii-alveolar-epithelial-cells-a549
#15
Esmaeil Mortaz, Shamila D Alipoor, Masoud Movassaghi, Mohammad Varahram, Jahangir Ghorbani, Gert Folkerts, Johan Garssen, Ian M Adcock
BACKGROUND: Tuberculosis (TB) is a major global health problem, and there is an association between tobacco smoke and TB. Water pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally because users consider it as safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be a predisposing factor that enhances the incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in alveolar epithelial cells following exposure to water-pipe smoke may predispose subjects to pulmonary infection...
April 21, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28424577/investigation-of-endocytic-pathways-for-the-internalization-of-exosome-associated-oligomeric-alpha-synuclein
#16
Marion Delenclos, Teodora Trendafilova, Divya Mahesh, Ann M Baine, Simon Moussaud, Irene K Yan, Tushar Patel, Pamela J McLean
Misfolding and aggregation of alpha-synuclein (αsyn) resulting in cytotoxicity is a hallmark of Parkinson's disease (PD) and related synucleinopathies. The recent body of evidence indicates that αsyn can be released from neuronal cells by nonconventional exocytosis involving extracellular vesicles (EVs) such as exosomes. The transfer of αsyn between cells has been proposed to be an important mechanism of disease propagation in PD. To date, exosome trafficking mechanisms, including release and cell-cell transmission, have not been fully described...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28416685/snat7-is-the-primary-lysosomal-glutamine-exporter-required-for-extracellular-protein-dependent-growth-of-cancer-cells
#17
Quentin Verdon, Marielle Boonen, Christopher Ribes, Michel Jadot, Bruno Gasnier, Corinne Sagné
Lysosomes degrade cellular components sequestered by autophagy or extracellular material internalized by endocytosis and phagocytosis. The macromolecule building blocks released by lysosomal hydrolysis are then exported to the cytosol by lysosomal transporters, which remain undercharacterized. In this study, we designed an in situ assay of lysosomal amino acid export based on the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis that detects lysosomal storage. This assay was used to screen candidate lysosomal transporters, leading to the identification of sodium-coupled neutral amino acid transporter 7 (SNAT7), encoded by the SLC38A7 gene, as a lysosomal transporter highly selective for glutamine and asparagine...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28402214/eyeing-autophagy-and-macropinocytosis-in-the-corneal-limbal-epithelia
#18
Han Peng, Jong Kook Park, Robert M Lavker
Macroautophagy/autophagy is vital for cellular homeostasis and helps cells respond to various stress situations. Macropinocytosis enables cells to nonselectively engulf and take up large volumes of fluid and is known to supply amino acids to cells. The stem cell-enriched limbal epithelium has the machinery necessary to carry out both autophagy and macropinocytosis; however, both processes are relatively understudied in this tissue. We have demonstrated that these processes are linked via MIR103-MIR107, a microRNA family that is limbal epithelial-preferred...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28391090/fast-and-ultrafast-endocytosis
#19
REVIEW
Shigeki Watanabe, Emmanuel Boucrot
Clathrin-mediated endocytosis (CME) is the main endocytic pathway supporting housekeeping functions in cells. However, CME may be too slow to internalize proteins from the cell surface during certain physiological processes such as reaction to stress hormones ('fight-or-flight' reaction), chemotaxis or compensatory endocytosis following exocytosis of synaptic vesicles or hormone-containing vesicles. These processes take place on a millisecond to second timescale and thus require very rapid cellular reaction to prevent overstimulation or exhaustion of the response...
April 5, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28389565/akt3-kinase-suppresses-pinocytosis-of-low-density-lipoprotein-by-macrophages-via-novel-wnk-sgk1-cdc42-pathway
#20
Liang Ding, Lifang Zhang, Michael Kim, Tatiana Byzova, Eugene Podrez
Fluid-phase pinocytosis of Low-density lipoprotein (LDL) by macrophages is regarded as a novel promising target to reduce macrophage cholesterol accumulation in atherosclerotic lesions. The mechanisms of regulation of fluid-phase pinocytosis in macrophages and specifically the role of Akt kinases are poorly understood. We have previously found that increased lipoprotein uptake via the receptor independent process in Akt3 kinase deficient macrophages contributes to increased atherosclerosis in Akt3-/- mice. The mechanism by which Akt3 deficiency promotes lipoprotein uptake in macrophages is unknown...
April 7, 2017: Journal of Biological Chemistry
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