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https://www.readbyqxmd.com/read/28226239/structural-basis-for-the-hijacking-of-endosomal-sorting-nexin-proteins-by-chlamydia-trachomatis
#1
Blessy Paul, Hyun Sung Kim, Markus C Kerr, Wilhelmina M Huston, Rohan D Teasdale, Brett M Collins
During infection chlamydial pathogens form an intracellular membrane-bound replicative niche termed the inclusion, which is enriched with bacterial transmembrane proteins called Incs. Incs bind and manipulate host cell proteins to promote inclusion expansion and provide camouflage against innate immune responses. Sorting nexin (SNX) proteins that normally function in endosomal membrane trafficking are a major class of inclusion-associated host proteins, and are recruited by IncE/CT116. Crystal structures of the SNX5 phox-homology (PX) domain in complex with IncE define the precise molecular basis for these interactions...
February 22, 2017: ELife
https://www.readbyqxmd.com/read/28225130/systematic-investigation-on-the-intracellular-trafficking-network-of-polymeric-nanoparticles
#2
Jinxie Zhang, Danfeng Chang, Yao Yang, Xudong Zhang, Wei Tao, Lijuan Jiang, Xin Liang, Hsiangi Tsai, Laiqiang Huang, Lin Mei
Polymeric nanoparticles such as PLGA-based nanoparticles are emerging as promising carriers for controlled drug delivery. However, little is known about the intracellular trafficking network of polymeric nanoparticles. Here, more than 30 Rab proteins were used as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy to investigate in detail the intracellular trafficking pathways of PLGA nanoparticles. We observed that coumarin-6-loaded PLGA nanoparticles were internalized by the cells mainly through caveolin and clathrin-dependent endocytosis and Rab34-mediated macropinocytosis...
February 22, 2017: Nanoscale
https://www.readbyqxmd.com/read/28224002/secretion-and-endocytosis-in-pollen-tubes-models-of-tip-growth-in-the-spot-light
#3
REVIEW
Gleb Grebnev, Maria Ntefidou, Benedikt Kost
Pollen tube tip growth is a widely used model ideally suited to study cellular processes underlying polarized cell expansion. Local secretion supplying material for plasma membrane (PM) and cell wall extension is essential for this process. Cell wall biogenesis requires fusion of secretory vesicles with the PM at an about 10× higher rate than PM extension. Excess material is therefore incorporated into the PM, which needs to be reinternalized through endocytosis. The classical model of tip growth proposes that exocytosis occurs at the apex and that newly incorporated PM material is transported to adjacent lateral regions, where excess material is endocytically recycled...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#4
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223800/comparison-of-the-cellular-transport-mechanism-of-cationic-star-shaped-polymers-and-liposomes-in-hacat-cells
#5
Heng-Cong Luo, Na Li, Li Yan, Kai-Jin Mai, Kan Sun, Wei Wang, Guo-Juan Lao, Chuan Yang, Li-Ming Zhang, Meng Ren
Several biological barriers must be overcome to achieve efficient nonviral gene delivery. These barriers include target cell uptake, lysosomal degradation, and dissociation from the carrier. In this study, we compared the differences in the uptake mechanism of cationic, star-shaped polymer/MMP-9siRNA complexes (β-CD-(D3)7/MMP-9siRNA complexes: polyplexes) and commercial liposome/MMP-9siRNA complexes (Lipofectamine(®) 2000/MMP-9siRNA complexes: liposomes). The uptake pathway and transfection efficiency of the polyplexes and liposomes were determined by fluorescence microscopy, flow cytometry, and reverse transcriptase-polymerase chain reaction...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28223219/trpm2-contributes-to-lpc-induced-intracellular-ca-2-influx-and-microglial-activation
#6
Heejin Jeong, Yong Ho Kim, Yunsin Lee, Sung Jun Jung, Seog Bae Oh
Microglia are the resident immune cells which become activated in some pathological conditions in central nervous system (CNS). Lysophosphatidylcholine (LPC), an endogenous inflammatory phospholipid, is implicated in immunomodulatory function of glial cells in the CNS. Although several studies uncovered that LPC induces intracellular Ca(2+) influx and morphologic change in microglia, there is still no direct evidence showing change of phosphorylation of mitogen-activated protein kinase (MAPK) p38 (p-p38), a widely used microglia activation marker, by LPC...
February 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28223095/palmitoylation-of-plasmodium-alveolins-promotes-cytoskeletal-function
#7
Annie Z Tremp, Fatimah S Al-Khattaf, Johannes T Dessens
S-palmitoylation is a post-translational lipid modification that is widespread among Plasmodium proteins and essential for parasite development. Little is known about the contribution of palmitoylation to the function of individual parasite molecules and structures. Alveolins are major components of the subpellicular network (SPN), a cortical cytoskeleton primarily involved in providing mechanical strength to the cell. We show here that the alveolin IMC1c is palmitoylated on a conserved cysteine motif, and that non-palmitoylated IMC1c displays normal expression, stability and trafficking...
February 18, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28222887/rare-er-protein-misfolding-mistrafficking-disorders-therapeutic-developments
#8
REVIEW
Ramanath Narayana Hegde, Advait Subramanian, Prathyush Pothukuchi, Seetharaman Parashuraman, Alberto Luini
The presence of a functional protein at the appropriate location in the cell is the result of the processes of transcription, translation, folding and trafficking to the correct destination. There are numerous diseases that are caused by protein misfolding, mainly due to mutations in the respective gene. The consequences of this misfolding may be that proteins effectively lose their function, either by being removed by the cellular quality control machinery or by accumulating at the incorrect intracellular or extracellular location...
February 9, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28222329/inflammatory-chemokines-and-their-receptors-in-human-visceral-leishmaniasis-gene-expression-profile-in-peripheral-blood-splenic-cellular-sources-and-their-impact-on-trafficking-of-inflammatory-cells
#9
Neetu Singh, Shyam Sundar
Chemokines play an important role in determining cellular composition at inflammatory sites, and as such, influence disease outcome. In this study, we investigated the expression profile and splenic cellular source of various inflammatory chemokines and their receptors in human visceral leishmaniasis (VL). The expression of chemokines or their receptors was measured at the gene and protein level by employing real time qPCR and a cytometric bead array assay, respectively. In addition, the cellular source of chemokines and their receptors in the spleen was identified employing gene expression analyses in sequentially selected cell subsets...
February 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28222213/rab7a-regulates-tau-secretion
#10
Lilia Rodriguez, Nguyen-Vi Mohamed, Alexandre Desjardins, Roger Lippé, Edward Fon, Nicole Leclerc
The axonal microtubule-associated protein TAU, involved in Alzheimer's disease (AD), can be found in the extracellular space where it could be taken up by neurons, an event that is believed to contribute to the propagation of tau pathology in the brain. Since the small GTPase Rab7A is involved in the trafficking of endosomes, autophagosomes and lysosomes, and RAB7A gene expression and protein levels are upregulated in AD patients, we tested the hypothesis that Rab7A was involved in Tau secretion. We previously reported that both primary cortical neurons and HeLa cells overexpressing human TAU can release Tau...
February 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28221136/an-essential-dual-function-complex-mediates-erythrocyte-invasion-and-channel-mediated-nutrient-uptake-in-malaria-parasites
#11
Daisuke Ito, Marc A Schureck, Sanjay A Desai
Malaria parasites evade immune detection by growth and replication within erythrocytes. After erythrocyte invasion, the intracellular pathogen must increase host cell uptake of nutrients from plasma. Here, we report that the parasite-encoded RhopH complex contributes to both invasion and channel-mediated nutrient uptake. As rhoph2 and rhoph3 gene knockouts were not viable in the human P. falciparum pathogen, we used conditional knockdowns to determine that the encoded proteins are essential and to identify their stage-specific functions...
February 21, 2017: ELife
https://www.readbyqxmd.com/read/28220989/global-and-local-mechanisms-sustain-axonal-proteostasis-of-transmembrane-proteins
#12
REVIEW
Víctor Hugo Cornejo, Alejandro Luarte, Andrés Couve
The control of neuronal protein homeostasis or proteostasis is tightly regulated both spatially and temporally, assuring accurate and integrated responses to external or intrinsic stimuli. Local or autonomous responses in dendritic and axonal compartments are crucial to sustain function during development, physiology and in response to damage or disease. Axons are responsible for generating and propagating electrical impulses in neurons, and the establishment and maintenance of their molecular composition are subject to extreme constraints exerted by length and size...
February 21, 2017: Traffic
https://www.readbyqxmd.com/read/28220142/absence-of-an-n-linked-glycosylation-motif-in-the-glycoprotein-of-the-live-attenuated-argentine-hemorrhagic-fever-vaccine-candid-1-results-in-its-improper-processing-and-reduced-surface-expression
#13
John T Manning, Alexey V Seregin, Nadezhda E Yun, Takaaki Koma, Cheng Huang, José Barral, Juan C de la Torre, Slobodan Paessler
Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. However, the mechanisms through which the GPC contributes to the attenuation of the Can strain remain unknown. A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28220121/bidirectional-crosstalk-between-lymphatic-endothelial-cell-and-t-cell-and-its-implications-in-tumor-immunity
#14
REVIEW
Kim Pin Yeo, Veronique Angeli
Lymphatic vessels have been traditionally considered as passive transporters of fluid and lipids. However, it is apparent from recent literature that the function of lymphatic vessels is not only restricted to fluid balance homeostasis but also extends to regulation of immune cell trafficking, antigen presentation, tolerance, and immunity, all which may impact the progression of inflammatory responses and diseases such as cancer. The lymphatic system and the immune system are intimately connected, and there is emergent evidence for a crosstalk between T cell and lymphatic endothelial cell (LEC)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219003/targeting-the-cxcl12-cxcr4-axis-in-acute-myeloid-leukemia-from-bench-to-bedside
#15
Byung-Sik Cho, Hee-Je Kim, Marina Konopleva
The interactions between the cancerous cells of acute myeloid leukemia (AML) and the bone marrow (BM) microenvironment have been postulated to be important for resistance to chemotherapy and disease relapse in AML. The chemokine receptor CXC chemokine receptor 4 (CXCR4) and its ligand, CXC motif ligand 12 (CXCL12), also known as stromal cell-derived factor 1α, are key mediators of this interaction. CXCL12 is produced by the BM microenvironment, binds and activates its cognate receptor CXCR4 on leukemic cells, facilitates leukemia cell trafficking and homing in the BM microenvironment, and keeps leukemic cells in close contact with the stromal cells and extracellular matrix that constitutively generate growth-promoting and anti-apoptotic signals...
February 21, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28218996/hypoxia-stimulated-membrane-trafficking-requires-t-plastin
#16
Marieke Wottawa, Stephanie Naas, Johannes Böttger, Gijsbert J van Belle, Wiebke Möbius, Natalia H Revelo, Doris Heidenreich, Melanie von Ahlen, Anke Zieseniss, Katharina Kröhnert, Susanne Lutz, Christof Lenz, Henning Urlaub, Silvio O Rizzoli, Dörthe M Katschinski
Traffic between the plasma membrane and the endomembrane compartments is an essential feature of eukaryotic cells. The secretory pathway sends cargoes from biosynthetic compartments to the plasma membrane. This is counterbalanced by a retrograde endocytotic route and is essential for cell homeostasis. Cells need to adapt rapidly to environmental challenges like the reduction of pO2 which, however, has not been analyzed in relation to membrane trafficking in detail. Therefore we determined changes in the plasma membrane trafficking in normoxia, hypoxia, and after reoxygenation METHODS: Membrane trafficking was analyzed by using the bulk membrane endocytosis marker FM 1-43, the newly developed membrane probe mCLING, wheat germ agglutinin as well as fluorescently labeled choleratoxin subunit B...
February 20, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28218918/transgenic-expression-of-human-apol1-risk-variants-in-podocytes-induces-kidney-disease-in-mice
#17
Pazit Beckerman, Jing Bi-Karchin, Ae Seo Deok Park, Chengxiang Qiu, Patrick D Dummer, Irfana Soomro, Carine M Boustany-Kari, Steven S Pullen, Jeffrey H Miner, Chien-An A Hu, Tibor Rohacs, Kazunori Inoue, Shuta Ishibe, Moin A Saleem, Matthew B Palmer, Ana Maria Cuervo, Jeffrey B Kopp, Katalin Susztak
African Americans have a heightened risk of developing chronic and end-stage kidney disease, an association that is largely attributed to two common genetic variants, termed G1 and G2, in the APOL1 gene. Direct evidence demonstrating that these APOL1 risk alleles are pathogenic is still lacking because the APOL1 gene is present in only some primates and humans; thus it has been challenging to demonstrate experimental proof of causality of these risk alleles for renal disease. Here we generated mice with podocyte-specific inducible expression of the APOL1 reference allele (termed G0) or each of the risk-conferring alleles (G1 or G2)...
February 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28218511/engineering-of-radioiodine-labeled-gold-core-shell-nanoparticles-as-efficient-nuclear-medicine-imaging-agents-for-trafficking-of-dendritic-cells
#18
Sang Bong Lee, Sang-Woo Lee, Shin Young Jeong, GhilSuk Yoon, Sung Jin Cho, Sang Kyoon Kim, In-Kyu Lee, Byeong-Cheol Ahn, Jaetae Lee, Yong Hyun Jeon
The development of highly sensitive, stable, and biocompatible imaging agents allowing visualization of dendritic cell (DC) migration is one of the essential factors for effective DC-based immunotherapy. Here, we used a novel and efficient synthesis approach to develop Radioiodine-124-labeled Tannic Acid Gold Core-Shell Nanoparticles (124I-TA-Au@AuNPs) for DC labeling and in vivo tracking of their migration using positron emission tomography (PET). 124I-TA-Au@AuNPs were produced within 40 min in high yield via straightforward tannic acid-mediated radiolabeling chemistry and incorporation of Au shell, which resulted in high radio-sensitivity and excellent chemical stability of nanoparticles in DCs and living mice...
February 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28218281/ubiquitination-and-dynactin-regulate-tmepai-lysosomal-trafficking
#19
Shenheng Luo, Lei Jing, Tian Zhao, Yuyin Li, Zhenxing Liu, Aipo Diao
The transmembrane prostate androgen-induced protein (TMEPAI) has been reported to be elevated in various tumor cells, is localized to the lysosome and promotes lysosome stability. The molecular mechanism of TMEPAI trafficking however to the lysosome is unknown. Here we report that clathrin and CI-M6PR mediate TMEPAI transport from the Golgi directly into the endo-lysosomal pathway. TMEPAI is ubiquitinated at its C-terminal region and ubiquitination modification of TMEPAI is a signal for its lysosomal trafficking...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217126/high-endothelial-venules-and-other-blood-vessels-critical-regulators-of-lymphoid-organ-development-and-function
#20
REVIEW
Ann Ager
The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer's patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues...
2017: Frontiers in Immunology
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