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Endocytic trafficking

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https://www.readbyqxmd.com/read/28537552/structure-analyses-reveal-a-regulated-oligomerization-mechanism-of-the-plexind1-gipc-myosin-vi-complex
#1
Guijun Shang, Chad A Brautigam, Rui Chen, Defen Lu, Jesús Torres-Vázquez, Xuewu Zhang
The GIPC family adaptor proteins mediate endocytosis by tethering cargo proteins to the myosin VI motor. The structural mechanisms for the GIPC/cargo and GIPC/myosin VI interactions remained unclear. PlexinD1, a transmembrane receptor that regulates neuronal and cardiovascular development, is a cargo of GIPCs. GIPC-mediated endocytic trafficking regulates PlexinD1 signaling. Here we unravel the mechanisms of the interactions among PlexinD1, GIPCs and myosin VI by a series of crystal structures of these proteins in apo or bound states...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28513921/chitin-induced-and-chitin-elicitor-receptor-kinase1-cerk1-phosphorylation-dependent-endocytosis-of-arabidopsis-thaliana-lysin-motif-containing-receptor-like-kinase5-lyk5
#2
Jan Erwig, Hassan Ghareeb, Michaela Kopischke, Ronja Hacke, Alexandra Matei, Elena Petutschnig, Volker Lipka
To detect potential pathogens, plants perceive the fungal polysaccharide chitin through receptor complexes containing lysin motif receptor-like kinases (LysM-RLKs). To investigate the ligand-induced spatial dynamics of chitin receptor components, we studied the subcellular behaviour of two Arabidopsis thaliana LysM-RLKs involved in chitin signalling, CHITIN ELICITOR RECEPTOR KINASE1 (CERK1) and LYSIN MOTIF-CONTAINING RECEPTOR-LIKE KINASE5. We performed standard and quantitative confocal laser scanning microscopy on stably transformed A...
May 17, 2017: New Phytologist
https://www.readbyqxmd.com/read/28507272/phosphatidylinositol-5-phosphate-4-kinase-regulates-early-endosomal-dynamics-during-clathrin-mediated-endocytosis
#3
Kumari Kamalesh, Deepti Trivedi, Sarah Toscano, Sanjeev Sharma, Sourav Kolay, Padinjat Raghu
Endocytic turnover is essential to regulate the protein composition and function of the plasma membrane thus regulating the plasma membrane levels of many receptors. In Drosophila photoreceptors, photon absorption by the GPCR rhodopsin 1 (Rh1) triggers its endocytosis by clathrin-mediated endocytosis (CME). We find that CME of Rh1 is regulated by phosphatidylinositol 5 phosphate 4-kinase (PIP4K). Flies lacking PIP4K show mislocalization of Rh1 on expanded endomembranes within the cell body. This mislocalization of Rh1 was dependent on the formation of an expanded Rab5 compartment...
May 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28504462/endocytic-activity-of-hiv-1-vpu-phosphoserine-dependent-interactions-with-clathrin-adaptors
#4
Charlotte A Stoneham, Rajendra Singh, Xiaofei Jia, Yong Xiong, John Guatelli
HIV-1 Vpu modulates cellular transmembrane proteins to optimize viral replication and provide immune-evasion, triggering ubiquitin-mediated degradation of some targets but also modulating endosomal trafficking to deplete them from the plasma membrane. Interactions between Vpu and the heterotetrameric clathrin adaptors AP-1 and AP-2 have been described, yet the molecular basis and functional roles of such interactions are incompletely defined. To investigate the trafficking signals encoded by Vpu, we fused the cytoplasmic domain (CD) of Vpu to the extracellular and transmembrane domains of the CD8 α-chain...
May 14, 2017: Traffic
https://www.readbyqxmd.com/read/28500977/endocytosis-and-intracellular-traffic-of-cholesterol-pdmaema-liposome-complexes-in-human-epithelial-like-cells
#5
F Szymanowski, A A Hugo, P Alves, P N Simões, A Gómez-Zavaglia, Pablo F Pérez
Liposomes are generally used as delivery systems, as they are capable of encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins, therapeutic drugs). However, liposomal drug delivery have to fulfill different requirements, such as the effective internalization by the target cells and avoidance of the degradative activity of the intracellular compartments. The use of polymer lipid complexes (PLCs), by including different polymers in the liposome formulation, could improve internalization and intracellular release of drugs...
May 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28493289/intestinal-epithelial-claudins-expression-and-regulation-in-homeostasis-and-inflammation
#6
REVIEW
Vicky Garcia-Hernandez, Miguel Quiros, Asma Nusrat
The intestinal epithelium forms a highly dynamic and selective barrier that controls absorption of fluid and solutes while restricting pathogen access to underlying tissues. Barrier properties are achieved by intercellular junctions that include an apical tight junction (TJ) and subjacent adherens junctions and desmosomes. The TJ tetraspan claudin proteins form pores between epithelial cells to control paracellular fluid and ion movement. In addition to regulation of barrier function, claudin family members control epithelial homeostasis and are expressed in a spatiotemporal manner in the intestinal crypt-luminal axis...
May 10, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28481347/membrane-curvature-regulates-ligand-specific-membrane-sorting-of-gpcrs-in-living-cells
#7
Kadla R Rosholm, Natascha Leijnse, Anna Mantsiou, Vadym Tkach, Søren L Pedersen, Volker F Wirth, Lene B Oddershede, Knud J Jensen, Karen L Martinez, Nikos S Hatzakis, Poul Martin Bendix, Andrew Callan-Jones, Dimitrios Stamou
The targeted spatial organization (sorting) of Gprotein-coupled receptors (GPCRs) is essential for their biological function and often takes place in highly curved membrane compartments such as filopodia, endocytic pits, trafficking vesicles or endosome tubules. However, the influence of geometrical membrane curvature on GPCR sorting remains unknown. Here we used fluorescence imaging to establish a quantitative correlation between membrane curvature and sorting of three prototypic class A GPCRs (the neuropeptide Y receptor Y2, the β1 adrenergic receptor and the β2 adrenergic receptor) in living cells...
May 8, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28468881/mutations-in-the-transmembrane-domain-and-cytoplasmic-tail-of-hendra-virus-fusion-protein-disrupt-virus-like-particle-assembly
#8
Nicolás Cifuentes-Muñoz, Weina Sun, Greeshma Ray, Phuong Tieu Schmitt, Stacy Webb, Kathleen Gibson, Rebecca Ellis Dutch, Anthony P Schmitt
Hendra virus (HeV) is a zoonotic paramyxovirus that causes deadly illness in horses and humans. An intriguing feature of HeV is the utilization of endosomal protease for activation of the viral fusion protein (F). Here, we investigated how F endosomal trafficking impacts HeV assembly. We found that HeV matrix (M) and F proteins each induced particle release when expressed alone, but their co-expression led to coordinated assembly of virus-like particles (VLPs) that were morphologically and physically distinct from M-alone or F-alone VLPs...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28462706/endocytosis-of-nanoscale-systems-for-cancer-treatments
#9
Kai Chen, Xue Li, Hongyan Zhu, Qiyong Gong, Kui Luo
Advances of nanoscale systems for cancer treatment have been involved in enabling highly regulated site-specific localization to sub cellular organelles hidden beneath cell membranes. Thus far, the cellular entry of these nanoscale systems has been not fully understood. Endocytosisis a form of active transport in which cell transports elected extracellular molecules (such as proteins, viruses, micro-organisms and nanoscale systems) are allowed into cell interiors by engulfing them in an energy-dependent process...
April 28, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28456978/quantitative-co-localization-and-pattern-analysis-of-endo-lysosomal-cargo-in-subcellular-image-cytometry-and-validation-on-synthetic-image-sets
#10
Frederik W Lund, Daniel Wüstner
Late endosomes and lysosomes (LE/LYSs) play a central role in trafficking of endocytic cargo, secretion of exosomes, and hydrolysis of ingested proteins and lipids. Failure in such processes can lead to lysosomal storage disorders in which a particular metabolite accumulates within LE/LYSs. Analysis of endocytic trafficking relies heavily on quantitative fluorescence microscopy, but evaluation of the huge image data sets is challenging and demands computer-assisted statistical tools. Here, we describe how to use SpatTrack ( www...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28456515/spatial-encryption-of-g-protein-coupled-receptor-signaling-in-endosomes-mechanisms-and-applications
#11
REVIEW
Silvia Sposini, Aylin C Hanyaloglu
Within any cellular signaling system membrane trafficking is a critical mechanism for cells to translate complex networks into specific downstream responses, including the signal pathways activated by the superfamily of G protein-coupled receptors (GPCRs). Classically, membrane trafficking is viewed as a mechanism to regulate ligand sensitivity of a target tissue by controlling the level of surface receptors. Recent studies, however, have not only highlighted that GPCR trafficking is a tightly regulated process critical for spatio-temporal control of signaling, but that heterotrimeric G protein signaling can also be reactivated or continue to signal from distinct endocytic compartments, and even endosomal microdomains...
April 27, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28455444/endophilin-b2-facilitates-endosome-maturation-in-response-to-growth-factor-stimulation-autophagy-induction-and-influenza-a-virus-infection
#12
Jacob M Serfass, Yoshinori Takahashi, Zhixiang Zhou, Yuka Imamura Kawasawa, Ying Liu, Nikolaos Tsotakos, Megan M Young, Zhenyuan Tang, Linlin Yang, Jennifer M Atkinson, Zissis C Chroneos, Hong-Gang Wang
Endocytosis, and the subsequent trafficking of endosomes, requires dynamic physical alterations in membrane shape that are mediated in part by endophilin proteins. The endophilin B family of proteins contains an N-terminal Bin/Amphiphysin/Rvs (N-BAR) domain that induces membrane curvature to regulate intracellular membrane dynamics. While endophilin B1 (SH3GLB1/Bif-1) is known to be involved in a number of cellular processes, including apoptosis, autophagy and endocytosis, the cellular function of endophilin B2 (SH3GLB2) is not well understood...
April 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28453831/sortilin-1-loss-of-function-protects-against-cholestatic-liver-injury-by-attenuating-hepatic-bile-acid-accumulation-in-bile-duct-ligated-mice
#13
Jibiao Li, Benjamin L Woolbright, Wen Zhao, Yifeng Wang, David Matye, Bruno Hagenbuch, Hartmut Jaeschke, Tiangang Li
Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid metabolism. This study further investigated the role of Sort1 in modulating bile acid detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 KO mice had attenuated liver injury 24 h after BDL, which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger bile acid pool size than sham-operated WT mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic bile acid accumulation and smaller bile acid pool size...
April 26, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28451521/t3ss-independent-uptake-of-the-short-trip-toxin-related-recombinant-nlec-effector-of-enteropathogenic-escherichia-coli-leads-to-nf-%C3%AE%C2%BAb-p65-cleavage
#14
Anne-Sophie Stolle, Stefanie Norkowski, Britta Körner, Jürgen Schmitz, Lena Lüken, Maj Frankenberg, Christian Rüter, M Alexander Schmidt
Effector proteins secreted by the type 3 secretion system (T3SS) of pathogenic bacteria have been shown to precisely modulate important signaling cascades of the host for the benefit of the pathogens. Among others, the non-LEE encoded T3SS effector protein NleC of enteropathogenic Escherichia coli (EPEC) is a Zn-dependent metalloprotease and suppresses innate immune responses by directly targeting the NF-κB signaling pathway. Many pathogenic bacteria release potent bacterial toxins of the A-B type, which-in contrast to the direct cytoplasmic injection of T3SS effector proteins-are released first into the environment...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28449134/characterizing-exogenous-mrna-delivery-trafficking-cytoplasmic-release-and-rna-protein-correlations-at-the-level-of-single-cells
#15
Jonathan L Kirschman, Sushma Bhosle, Daryll Vanover, Emmeline L Blanchard, Kristin H Loomis, Chiara Zurla, Kathryn Murray, Blaine C Lam, Philip J Santangelo
The use of synthetic messenger ribonucleic acid (mRNA) to express specific proteins is a highly promising therapeutic and vaccine approach that avoids many safety issues associated with viral or DNA-based systems. However, in order to optimize mRNA designs and delivery, technology advancements are required to study fundamental mechanisms of mRNA uptake and localization at the single-cell and tissue level. Here, we present a single RNA sensitive fluorescent labeling method which allows us to label and visualize synthetic mRNA without significantly affecting function...
April 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28445739/autophagy-associated-cytotoxicity-and-cellular-uptake-mechanisms-of-bismuth-nanoparticles-in-human-kidney-cells
#16
Yongming Liu, Jing Zhuang, Xihui Zhang, Cong Yue, Ning Zhu, Liecheng Yang, Yong Wang, Tao Chen, Yangyun Wang, Leshuai W Zhang
Bismuth compounds have been used for treatment of bacterial infection, and recently bismuth nanoparticles (BiNP) were synthesized for imaging and diagnostic purpose, while safety concern of bismuth cannot be ignored. Here, we prepared ultrasmall BiNP and showed an enhanced tumor imaging, but BiNP revealed a differentiated cytotoxicity in human embryonic kidney 293 cells (HEK293) compared to other cell types. For the first time, we found that BiNP can induce autophagy, shown as the increase of monodansylcadaverine fluorescence staining and the amount of LC3II that can be inhibited by 3-MA...
April 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28436498/integrative-meta-modeling-identifies-endocytic-vesicles-late-endosome-and-the-nucleus-as-the-cellular-compartments-primarily-directing-rtk-signaling
#17
Jared C Weddell, Princess I Imoukhuede
Recently, intracellular receptor signaling has been identified as a key component mediating cell responses for various receptor tyrosine kinases (RTKs). However, the extent each endocytic compartment (endocytic vesicle, early endosome, recycling endosome, late endosome, lysosome and nucleus) contributes to receptor signaling has not been quantified. Furthermore, our understanding of endocytosis and receptor signaling is complicated by cell- or receptor-specific endocytosis mechanisms. Therefore, towards understanding the differential endocytic compartment signaling roles, and identifying how to achieve signal transduction control for RTKs, we delineate how endocytosis regulates RTK signaling...
May 22, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28434950/an-arabidopsis-lipid-flippase-is-required-for-timely-recruitment-of-defenses-to-the-host-pathogen-interface-at-the-plant-cell-surface
#18
William Underwood, Andrew Ryan, Shauna C Somerville
Deposition of cell wall-reinforcing papillae is an integral component of the plant immune response. The Arabidopsis PENETRATION 3 (PEN3) ATP binding cassette (ABC) transporter plays a role in defense against numerous pathogens and is recruited to sites of pathogen detection where it accumulates within papillae. However, the trafficking pathways and regulatory mechanisms contributing to recruitment of PEN3 and other defenses to the host-pathogen interface are poorly understood. Here, we report a confocal microscopy-based screen to identify mutants with altered localization of PEN3-GFP after inoculation with powdery mildew fungi...
April 18, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28424577/investigation-of-endocytic-pathways-for-the-internalization-of-exosome-associated-oligomeric-alpha-synuclein
#19
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/28422978/the-escrt-regulator-did2-maintains-the-balance-between-long-distance-endosomal-transport-and-endocytic-trafficking
#20
Carl Haag, Thomas Pohlmann, Michael Feldbrügge
In highly polarised cells, like fungal hyphae, early endosomes function in both endocytosis as well as long-distance transport of various cargo including mRNA and protein complexes. However, knowledge on the crosstalk between these seemingly different trafficking processes is scarce. Here, we demonstrate that the ESCRT regulator Did2 coordinates endosomal transport in fungal hyphae of Ustilago maydis. Loss of Did2 results in defective vacuolar targeting, less processive long-distance transport and abnormal shuttling of early endosomes...
April 2017: PLoS Genetics
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