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https://www.readbyqxmd.com/read/28934248/vps35-deficiency-impairs-slc4a11-trafficking-and-promotes-corneal-dystrophy
#1
Wei Liu, Fu-Lei Tang, Sen Lin, Kai Zhao, Lin Mei, Jian Ye, Wen-Cheng Xiong
Vps35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD). However, Vps35/retromer's function in the eye or the contribution of Vps35-deficiency to eye degenerative disorders remains to be explored. Here we provide evidence for a critical role of Vps35 in mouse corneal dystrophy. Vps35 is expressed in mouse and human cornea...
2017: PloS One
https://www.readbyqxmd.com/read/28934222/endogenous-rgs14-is-a-cytoplasmic-nuclear-shuttling-protein-that-localizes-to-juxtanuclear-membranes-and-chromatin-rich-regions-of-the-nucleus
#2
Mary Rose Branch, John R Hepler
Regulator of G protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates G protein and H-Ras/MAPkinase signaling pathways to regulate synaptic plasticity important for hippocampal learning and memory. However, to date, little is known about the subcellular distribution and roles of endogenous RGS14 in a neuronal cell line. Most of what is known about RGS14 cellular behavior is based on studies of tagged, recombinant RGS14 ectopically overexpressed in unnatural host cells. Here, we report for the first time a comprehensive assessment of the subcellular distribution and dynamic localization of endogenous RGS14 in rat B35 neuroblastoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/28934205/a-rab5-gtpase-module-is-important-for-autophagosome
#3
Fan Zhou, Shenshen Zou, Yong Chen, Zhanna Lipatova, Dan Sun, Xiaolong Zhu, Rui Li, Zulin Wu, Weiming You, Xiaoxia Cong, Yiting Zhou, Zhiping Xie, Valeriya Gyurkovska, Yutao Liu, Qunli Li, Wenjing Li, Jie Cheng, Yongheng Liang, Nava Segev
In the conserved autophagy pathway, the double-membrane autophagosome (AP) engulfs cellular components to be delivered for degradation in the lysosome. While only sealed AP can productively fuse with the lysosome, the molecular mechanism of AP closure is currently unknown. Rab GTPases, which regulate all intracellular trafficking pathways in eukaryotes, also regulate autophagy. Rabs function in GTPase modules together with their activators and downstream effectors. In yeast, an autophagy-specific Ypt1 GTPase module, together with a set of autophagy-related proteins (Atgs) and a phosphatidylinositol-3-phosphate (PI3P) kinase, regulates AP formation...
September 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28933412/genetic-substrate-reduction-therapy-a-promising-approach-for-lysosomal-storage-disorders
#4
REVIEW
Maria Francisca Coutinho, Juliana Inês Santos, Liliana Matos, Sandra Alves
Lysosomal storage diseases are a group of rare genetic disorders characterized by the accumulation of storage molecules in late endosomes/lysosomes. Most of them result from mutations in genes encoding for the catabolic enzymes that ensure intralysosomal digestion. Conventional therapeutic options include enzyme replacement therapy, an approach targeting the functional loss of the enzyme by injection of a recombinant one. Even though this is successful for some diseases, it is mostly effective for peripheral manifestations and has no impact on neuropathology...
November 9, 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/28932708/intracellular-trafficking-pathways-of-edwardsiella-tarda-from-clathrin-and-caveolin-mediated-endocytosis-to-endosome-and-lysosome
#5
Zhi-Hai Sui, Haijiao Xu, Hongda Wang, Shuai Jiang, Heng Chi, Li Sun
Edwardsiella tarda is a Gram-negative bacterium that can infect a broad range of hosts including humans and fish. Accumulating evidences have indicated that E. tarda is able to survive and replicate in host phagocytes. However, the pathways involved in the intracellular infection of E. tarda are unclear. In this study, we examined the entry and endocytic trafficking of E. tarda in the mouse macrophage cell line RAW264.7. We found that E. tarda entered RAW264.7 and multiplied intracellularly in a robust manner...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28932622/high-throughput-nuclear-delivery-and-rapid-expression-of-dna-via-mechanical-and-electrical-cell-membrane-disruption
#6
Xiaoyun Ding, Martin Stewart, Armon Sharei, James C Weaver, Robert S Langer, Klavs F Jensen
Nuclear transfection of DNA into mammalian cells is challenging yet critical for many biological and medical studies. Here, by combining cell squeezing and electric-field-driven transport in a device that integrates microfluidic channels with constrictions and microelectrodes, we demonstrate nuclear delivery of plasmid DNA within 1 hour after treatment, the most rapid DNA expression in a high-throughput setting (up to millions of cells per minute per device). Passing cells at high speed through microfluidic constrictions smaller than the cell diameter mechanically disrupts the cell membrane, allowing a subsequent electric field to further disrupt the nuclear envelope and drive DNA molecules into the cytoplasm and nucleus...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/28931724/vps18-recruits-vps41-to-the-human-hops-complex-via-a-ring-ring-interaction
#7
Morag Hunter, Edward J Scourfield, Edward Emmott, Stephen C Graham
Eukaryotic cells use conserved multisubunit membrane tethering complexes, including CORVET and HOPS, to control the fusion of endomembranes. These complexes have been extensively studied in yeast, but to date there have been far fewer studies of metazoan CORVET and HOPS. Both of these complexes comprise six subunits: a common four-subunit core and two unique subunits. Once assembled, these complexes function to recognise specific endosomal membrane markers and facilitate SNARE-mediated membrane fusion. CORVET promotes the homotypic fusion of early endosomes, while HOPS promotes the fusion of lysosomes to late endosomes and autophagosomes...
September 20, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28931594/adhesion-force-and-attachment-lifetime-of-the-kif16b-px-domain-interaction-with-lipid-membranes
#8
Serapion Pyrpassopoulos, Henry Shuman, E Michael Ostap
KIF16B is a highly processive kinesin-3 family member that participates in the trafficking and tubulation of early endosomes along microtubules. KIF16B attaches to lipid cargos via a PX motif at its C-terminus, which has nanomolar affinity for bilayers containing phosphatidylinositol-3-phosphate (PI(3)P). As the PX domain has been proposed to be a primary mechanical anchor for the KIF16B-cargo attachment, we measured the adhesion forces and detachment kinetics of the PX domain as it interacts with membranes containing 2% PI(3)P and 98% phosphatidylcholine...
September 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28928743/the-toll-for-trafficking-toll-like-receptor-7-delivery-to-the-endosome
#9
REVIEW
Carlene Petes, Natalya Odoardi, Katrina Gee
Toll-like receptor (TLR)-7 is an endosomal innate immune sensor capable of detecting single-stranded ribonucleic acid. TLR7-mediated induction of type I interferon and other inflammatory cytokine production is important in antiviral immune responses. Furthermore, altered TLR7 expression levels are implicated in various autoimmune disorders, indicating a key role for this receptor in modulating inflammation. This review is focused on the regulation of TLR7 expression and localization compared to that of the other endosomal TLRs: TLR3, 8, and 9...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928133/a-new-rab7-effector-controls-phosphoinositide-conversion-in-endosome-maturation
#10
James E Casanova, Bettina Winckler
Endosome maturation requires a coordinated change in the Rab GTPase and phosphoinositide composition of the endosomal membrane. In this issue, Liu et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201705151) identify WDR91 as a ubiquitous Rab7 effector that inhibits phosphatidylinositol 3-kinase activity on endosomes and is critical for endosome maturation, viability, and dendrite growth of neurons in vivo.
September 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28928016/cxcl14-acts-as-a-specific-carrier-of-cpg-dna-into-dendritic-cells-and-activates-toll-like-receptor-9-mediated-adaptive-immunity
#11
Kosuke Tanegashima, Rena Takahashi, Hideko Nuriya, Rina Iwase, Naoto Naruse, Kohei Tsuji, Akira Shigenaga, Akira Otaka, Takahiko Hara
CXCL14 is a primordial chemokine that plays multiple roles in tumor suppression, autoimmune arthritis, and obesity-associated insulin resistance. However, the underlying molecular mechanisms are unclear. Here, we show that CXCL14 transports various types of CpG oligodeoxynucleotide (ODN) into the endosomes and lysosomes of bone marrow-derived dendritic cells (DCs), thereby activating Toll-like receptor 9 (TLR9). A combination of CpG ODN (ODN2395) plus CXCL14 induced robust production of IL-12 p40 by wild-type, but not Tlr9-knockout, DCs...
September 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28927665/fgd5-sustains-vascular-endothelial-growth-factor-a-vegfa-signaling-through-inhibition-of-proteasome-mediated-vegf-receptor-2-degradation
#12
Johan Heldin, Paul O'Callaghan, Rodrigo Hernández Vera, Peder Fredlund Fuchs, Pär Gerwins, Johan Kreuger
The complete repertoire of endothelial functions elicited by FGD5, a guanine nucleotide exchange factor activating the Rho GTPase Cdc42, has yet to be elucidated. Here we explore FGD5's importance during vascular endothelial growth factor A (VEGFA) signaling via VEGF receptor 2 (VEGFR2) in human endothelial cells. In microvascular endothelial cells, FGD5 is located at the inner surface of the cell membrane as well as at the outer surface of EEA1-positive endosomes carrying VEGFR2. The latter finding prompted us to explore if FGD5 regulates VEGFR2 dynamics...
September 16, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28926622/a-high-mitochondrial-transport-rate-characterizes-cns-neurons-with-high-axonal-regeneration-capacity
#13
Romain Cartoni, Gulcin Pekkurnaz, Chen Wang, Thomas L Schwarz, Zhigang He
Improving axonal transport in the injured and diseased central nervous system has been proposed as a promising strategy to improve neuronal repair. However, the contribution of each cargo to the repair mechanism is unknown. DRG neurons globally increase axonal transport during regeneration. Because the transport of specific cargos after axonal insult has not been examined systematically in a model of enhanced regenerative capacity, it is unknown whether the transport of all cargos would be modulated equally in injured central nervous system neurons...
2017: PloS One
https://www.readbyqxmd.com/read/28926616/co-ordinated-activation-of-classical-and-novel-pkc-isoforms-is-required-for-pma-induced-mtorc1-activation
#14
Mengling Liu, Christopher J Clarke, Mohamed F Salama, Yeon Ja Choi, Lina M Obeid, Yusuf A Hannun
Protein kinase C (PKC) has been shown to activate the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, a central hub in the regulation of cell metabolism, growth and proliferation. However, the mechanisms by which PKCs activate mTORC1 are still ambiguous. Our previous study revealed that activation of classical PKCs (cPKC) results in the perinuclear accumulation of cPKC and phospholipase D2 (PLD2) in recycling endosomes in a PLD2-dependent manner. Here, we report that mTORC1 activation by phorbol 12,13-myristate acetate (PMA) requires both classic, cPKC, and novel PKC (nPKC) isoforms, specifically PKCη, acting through distinct pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28924139/srphi-ratiometric-ph-biosensors-for-super-resolution-microscopy
#15
Douglas S Richardson, Carola Gregor, Franziska R Winter, Nicolai T Urban, Steffen J Sahl, Katrin I Willig, Stefan W Hell
Fluorescence-based biosensors have become essential tools for modern biology, allowing real-time monitoring of biological processes within living cells. Intracellular fluorescent pH probes comprise one of the most widely used families of biosensors in microscopy. One key application of pH probes has been to monitor the acidification of vesicles during endocytosis, an essential function that aids in cargo sorting and degradation. Prior to the development of super-resolution fluorescence microscopy (nanoscopy), investigation of endosomal dynamics in live cells remained difficult as these structures lie at or below the ~250 nm diffraction limit of light microscopy...
September 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28924047/endothelial-rab7-gtpase-mediates-tumor-growth-and-metastasis-in-lysosomal-acid-lipase-deficient-mice
#16
Ting Zhao, Xinchun Ding, Cong Yan, Hong Du
Tumors depend on their microenvironment for sustained growth, invasion and metastasis. In this environment, endothelial cells (ECs) are an important stromal cell type interacting with malignant cells to facilitate tumor angiogenesis and cancer cell extravasation. Of note, lysosomal acid lipase (LAL) deficiency facilitates melanoma growth and metastasis. ECs from LAL-deficient (lal-/-) mice possess enhanced proliferation, migration, and permeability of inflammatory cells by activating the mammalian target of rapamycin (mTOR) pathway...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28923824/snapin-promotes-hiv-1-transmission-from-dendritic-cells-by-dampening-tlr8-signaling
#17
Elham Khatamzas, Madeleine Maria Hipp, Daniel Gaughan, Tica Pichulik, Alasdair Leslie, Ricardo A Fernandes, Daniele Muraro, Sarah Booth, Kieran Zausmer, Mei-Yi Sun, Benedikt Kessler, Sarah Rowland-Jones, Vincenzo Cerundolo, Alison Simmons
HIV-1 traffics through dendritic cells (DCs) en route to establishing a productive infection in T lymphocytes but fails to induce an innate immune response. Within DC endosomes, HIV-1 somehow evades detection by the pattern-recognition receptor (PRR) Toll-like receptor 8 (TLR8). Using a phosphoproteomic approach, we identified a robust and diverse signaling cascade triggered by HIV-1 upon entry into human DCs. A secondary siRNA screen of the identified signaling factors revealed several new mediators of HIV-1 trans-infection of CD4(+) T cells in DCs, including the dynein motor protein Snapin...
September 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28922401/rab11-family-expression-in-the-human-placenta-localization-at-the-maternal-fetal-interface
#18
Elizabeth S Taglauer, Patrycja A Artemiuk, Sara R Hanscom, Andrew J Lindsay, Danielle Wuebbolt, Fionnuala M Breathnach, Elizabeth C Tully, Amir R Khan, Mary W McCaffrey
Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting...
2017: PloS One
https://www.readbyqxmd.com/read/28922372/reduction-of-organelle-motility-by-removal-of-potassium-and-other-solutes
#19
John W Murray, David Yin, Allan W Wolkoff
There are surprisingly few studies that describe how the composition of cell culture medium may affect the trafficking of organelles. Here we utilize time lapse multi-channel fluorescent imaging to show that short term exposure of Huh-7 cells to medium lacking potassium, sodium, or chloride strongly reduces but does not eliminate the characteristic back and forth and cell-traversing movement of fluorescent EGF (FL-EGF) containing organelles. We focused on potassium because of its relatively low abundance in media and serum and its energy requiring accumulation into cells...
2017: PloS One
https://www.readbyqxmd.com/read/28919207/phospho-regulation-of-soma-to-axon-transcytosis-of-neurotrophin-receptors
#20
Naoya Yamashita, Rajshri Joshi, Sheng Zhang, Zhong-Yin Zhang, Rejji Kuruvilla
Axonal targeting of signaling receptors is essential for neuronal responses to extracellular cues. Here, we report that retrograde signaling by target-derived nerve growth factor (NGF) is necessary for soma-to-axon transcytosis of TrkA receptors in sympathetic neurons, and we define the molecular underpinnings of this positive feedback regulation that enhances neuronal sensitivity to trophic factors. Activated TrkA receptors are retrogradely transported in signaling endosomes from distal axons to cell bodies, where they are inserted on soma surfaces and promote phosphorylation of resident naive receptors, resulting in their internalization...
September 9, 2017: Developmental Cell
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