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Kirsten Sandvig, Simona Kavaliauskiene, Tore Skotland
This article aims at providing an update on the complexity of clathrin-independent endocytosis. It is now almost 30 years since we first wrote a review about its existence; at that time many people believed that with the exception of macropinocytosis, which will only be briefly mentioned in this review, all uptake could be accounted for by clathrin-dependent endocytosis. Now it is generally accepted that there are different clathrin-independent mechanisms, some of them regulated by ligands and membrane lipid composition...
May 17, 2018: Histochemistry and Cell Biology
Yun-Na Zhang, Ya-Yun Liu, Fu-Chuan Xiao, Chun-Chun Liu, Xiao-Dong Liang, Jing Chen, Jing Zhou, Abdul Sattar Baloch, Lin Kan, Bin Zhou, Hua-Ji Qiu
The members of Flaviviridae utilize several endocytic pathways to enter a variety of host cells. Our previous work showed that classical swine fever virus (CSFV) enters porcine kidney (PK-15) cells through a clathrin-dependent pathway that requires Rab5 and Rab7. The entry mechanism for CSFV into other cell lines remains unclear, for instance, porcine alveolar macrophages (3D4/21 cells). More importantly, the trafficking of CSFV within endosomes controlled by Rab GTPases is unknown in 3D4/21 cells. In this study, entry and post-internalization of CSFV were analyzed using chemical inhibitors, RNA interference, and dominant negative (DN) mutants...
May 16, 2018: Journal of Virology
Xiaofei Wang, Weijin Sheng, Yangyang Wang, Liang Li, Yi Li, Shenghua Zhang, Xiujun Liu, Shuzhen Chen, Yongsu Zhen
Enhanced macropinocytosis has been found in K-Ras mutant pancreatic cancer cells and through which albumin can massively enter into the K-Ras driven cancer cells suggesting its role serving as micropinocytosis-intensifying drug delivery carrier. In the present study, a novel recombinant protein Fv-LDP-D3 and its reconstituted analogue Fv-LDP-D3-AE were designed and prepared. In which, Fv is the fragment of an anti-EGFR antibody, D3 is the domain III of HSA, LDP is the apoprotein of the antitumor antibiotic lidamycin (LDM), and AE is an extremely cytotoxic enediyne derived from LDM...
May 14, 2018: Molecular Pharmaceutics
Charlotte Ford, Andrea Nans, Emmanuel Boucrot, Richard D Hayward
Pathogens hijack host endocytic pathways to force their own entry into eukaryotic target cells. Many bacteria either exploit receptor-mediated zippering or inject virulence proteins directly to trigger membrane reorganisation and cytoskeletal rearrangements. By contrast, extracellular C. trachomatis elementary bodies (EBs) apparently employ facets of both the zipper and trigger mechanisms and are only ~400 nm in diameter. Our cryo-electron tomography of C. trachomatis entry revealed an unexpectedly diverse array of host structures in association with invading EBs, suggesting internalisation may progress by multiple, potentially redundant routes or several sequential events within a single pathway...
May 4, 2018: PLoS Pathogens
Victoire Gouirand, Fabienne Guillaumond, Sophie Vasseur
As with castles, tumor cells are fortified by surrounding non-malignant cells, such as cancer-associated fibroblasts, immune cells, but also nerve fibers and extracellular matrix. In most cancers, this fortification creates a considerable solid pressure which limits oxygen and nutrient delivery to the tumor cells and causes a hypoxic and nutritional stress. Consequently, tumor cells have to adapt their metabolism to survive and proliferate in this harsh microenvironment. To satisfy their need in energy and biomass, tumor cells develop new capacities to benefit from metabolites of the microenvironment, either by their uptake through the macropinocytosis process or through metabolite transporters, or by a cross-talk with stromal cells and capture of extracellular vesicles that are released by the neighboring cells...
2018: Frontiers in Oncology
Chunlei Zhang, Amin Zhang, Wenxiu Hou, Tianliang Li, Kan Wang, Qian Zhang, Jesús M De La Fuente, Weilin Jin, Daxiang Cui
Biological systems provide the richest spectrum of sophisticated design for materials engineering. We herein provide a paradigm of Au22 (SG)18 -(SG, glutathione thiolate)-engineered and hydrogen bonds engaged assemblies for mimicking capsid protein self-assembly. The water-evaporation-induced self-assembly method allows discrete ultrasmall gold nanoclusters (GNCs) to be self-assembled into super-GNCs assemblies (SGNCs) ranging from nano-, meso- to microscale in water-dimethylsulfoxide binary solvents in a template-free manner...
May 3, 2018: ACS Nano
Rebecca Kelsey
No abstract text is available yet for this article.
April 30, 2018: Nature Reviews. Urology
Douglas E Biancur, Alec C Kimmelman
Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer that is highly refractory to the current standards of care. The difficulty in treating this disease is due to a number of different factors, including altered metabolism. In PDA, the metabolic rewiring favors anabolic reactions which supply the cancer cell with necessary cellular building blocks for unconstrained growth. Furthermore, PDA cells display high levels of basal autophagy and macropinocytosis. KRAS is the driving oncogene in PDA and many of the metabolic changes are downstream of its activation...
April 24, 2018: Biochimica et Biophysica Acta
Emmanuelle R Quemin, Simon Corroyer-Dulmont, Jacomine Krijnse-Locker
Nucleocytoplasmic large DNA viruses (NCLDVs) are a steadily growing group of viruses that infect a wide range of hosts and are characterized by large particle dimensions and genome sizes. Understanding how they enter into the host cell and deliver their genome in the cytoplasm is therefore particularly intriguing. Here, we review the current knowledge on the entry of two of the best-characterized NCLDVs: the poxvirus Vaccinia virus (VACV) and the giant virus Mimivirus. While previous studies on VACV had proposed both direct fusion at the plasma membrane and endocytosis as entry routes, more recent biochemical and morphological data argue for macropinocytosis as well...
April 24, 2018: Journal of Molecular Biology
Samuel Alvarez-Arguedas, Santiago Uranga, Manuel Martín, Javier Elizalde, Ana Belen Gomez, Esther Julián, Denise Nardelli-Haefliger, Carlos Martín, Nacho Aguilo
Intravesical instillation of bacillus Calmette-Guérin (BCG) has been a first-line therapy for non-muscle-invasive bladder cancer for the last 4 decades. However, this treatment causes serious adverse events in a significant number of patients and a substantial percentage of recurrence episodes. MTBVAC is a live-attenuated vaccine derived from a Mycobacterium tuberculosis clinical isolate and is currently under evaluation in clinical trials to replace BCG as a tuberculosis vaccine. Here, we describe for the first time the potential of MTBVAC as a bladder cancer therapy in vitro and in vivo in a preclinical model...
April 6, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Jie Zhou, Aisha Roshan Mohamed Wali, Shengnan Ma, Yiyan He, Dong Yue, James Zhenggui Tang, Zhongwei Gu
In the progress of designing a gene carrier system, what is urgently needed is a balance of excellent safety and satisfactory efficiency. Herein, a straightforward and versatile synthesis of a cationic guanidine-decorated dendronized pullulan (OGG3P) for efficient genetic photodynamic therapy was proposed. OGG3P was able to block the mobility of DNA from a weight ratio of 2. However, G3P lacking guanidine residues could not block DNA migration until at a weight ratio of 15, revealing guanidination could facilitate DNA condensation via specific guanidinium-phosphate interactions...
April 24, 2018: Biomacromolecules
Claudia Hinze, Emmanuel Boucrot
Extracellular macromolecules, pathogens and cell surface proteins rely on endocytosis to enter cells. Key steps of endocytic carrier formation are cargo molecule selection, plasma membrane folding and detachment from the cell surface. While dedicated proteins mediate each step, the actin cytoskeleton contributes to all. However, its role can be indirect to the actual molecular events driving endocytosis. Here, we review our understanding of the molecular steps mediating local actin polymerization during the formation of endocytic carriers...
April 20, 2018: Biochemical Society Transactions
Andrew T Frawley, Holly V Linford, Matthieu Starck, Robert Pal, David Parker
The selective mitochondrial localisation of the Λ enantiomer of three different emissive europium(iii) complexes in NIH 3T3 and MCF7 cells contrasts with the behaviour of the Δ enantiomer, for which a predominant lysosomal localisation was observed by confocal microscopy. In each case, cell uptake occurs via macropinocytosis.
January 28, 2018: Chemical Science
Lijuan Jiang, Xin Liang, Gan Liu, Yun Zhou, Xinyu Ye, Xiuli Chen, Qianwei Miao, Li Gao, Xudong Zhang, Lin Mei
Protein nanocapsules have exhibited promising potential applications in the field of protein drug delivery. A major issue with various promising nano-sized biotherapeutics including protein nanocapsules is that owing to their particle size they are subject to cellular uptake via endocytosis, and become entrapped and then degraded within endolysosomes, which can significantly impair their therapeutic efficacy. In addition, many nano-sized biotherapeutics could be also sequestered by autophagosomes and degraded through the autolysosomal pathway...
November 2018: Drug Delivery
Lixiang Sun, Xiaohui Xu, Yongjun Chen, Yuxia Zhou, Ran Tan, Hantian Qiu, Liting Jin, Wenyi Zhang, Rong Fan, Wanjin Hong, Tuanlao Wang
The small GTPase Rab34 regulates spatial distribution of the lysosomes, secretion, and macropinocytosis. In this study, we found that Rab34 is over-expressed in aggressive breast cancer cells, implying a potential role of Rab34 in breast cancer. Silencing Rab34 by shRNA inhibits cell migration, invasion, and adhesion of breast cancer cells. Rab34 specifically binds to the cytoplasmic tail of integrin β3, and depletion of Rab34 promotes the degradation of integrin β3. Interestingly, EGF induces the translocation of Rab34 to the membrane ruffle, which is greatly enhanced by the expression of Src kinase...
April 6, 2018: Oncogene
Wenjing Huang, Yan Lang, Abdul Hakeem, Yan Lei, Lu Gan, Xiangliang Yang
Background: Multidrug resistance (MDR) is one of the major obstacles to successful cancer chemotherapy. Developing efficient strategies to reverse MDR remains a major challenge. Surfactin (SUR), a cyclic lipopeptide biosurfactant, has been found to display anticancer activity. Methods: In this paper, SUR was assembled by solvent-emulsion method to load the anticancer drug doxorubicin (DOX). The cytotoxicity of DOX-loaded SUR nanoparticles (DOX@SUR) against DOX-resistant human breast cancer MCF-7/ADR is measured by MTT assay...
2018: International Journal of Nanomedicine
Lewis D Evans, Thomas Wassmer, Graham Fraser, James Smith, Michael Perkinton, Andrew Billinton, Frederick J Livesey
In Alzheimer's disease, neurofibrillary tangle pathology appears to spread along neuronal connections, proposed to be mediated by the release and uptake of abnormal, disease-specific forms of microtubule-binding protein tau MAPT. It is currently unclear whether transfer of tau between neurons is a toxic gain-of-function process in dementia or reflects a constitutive biological process. We report two entry mechanisms for monomeric tau to human neurons: a rapid dynamin-dependent phase typical of endocytosis and a second, slower actin-dependent phase of macropinocytosis...
March 27, 2018: Cell Reports
Mohit P Mathew, Julie G Donaldson
Clathrin-independent endocytosis (CIE) is a form of endocytosis that lacks a defined cytoplasmic machinery. Here, we asked whether glycan interactions, acting from the outside, could be a part of that endocytic machinery. We show that the perturbation of global cellular patterns of protein glycosylation by modulation of metabolic flux affects CIE. Interestingly, these changes in glycosylation had cargo-specific effects. For example, in HeLa cells, N-acetylglucosamine treatment, which increases glycan branching, increased major histocompatibility complex class I (MHCI) internalization but inhibited CIE of the glycoprotein CD59 molecule (CD59)...
March 26, 2018: Journal of Biological Chemistry
(no author information available yet)
No abstract text is available yet for this article.
March 23, 2018: Journal of Cell Science
Seong M Kim, Tricia T Nguyen, Archna Ravi, Peter Kubiniok, Brendan T Finicle, Vaishali Jayashankar, Leonel Malacrida, Jue Hou, Jane Robertson, Dong Gao, Jonathan Chernoff, Michelle A Digman, Eric O Potma, Bruce J Tromberg, Pierre Thibault, Aimee L Edinger
We report that PTEN-deficient prostate cancer cells use macropinocytosis to survive and proliferate under nutrient stress. PTEN loss increased macropinocytosis only in the context of AMPK activation revealing a general requirement for AMPK in macropinocytosis and a novel mechanism by which AMPK promotes survival under stress. In prostate cancer cells, albumin uptake did not require macropinocytosis, but necrotic cell debris proved a specific macropinocytic cargo. Isotopic labeling confirmed that macropinocytosed necrotic cell proteins fueled new protein synthesis in prostate cancer cells...
March 23, 2018: Cancer Discovery
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