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https://www.readbyqxmd.com/read/29146912/structural-insights-into-legionella-ridl-vps29-retromer-subunit-interaction-reveal-displacement-of-the-regulator-tbc1d5
#1
Kevin Bärlocher, Cedric A J Hutter, A Leoni Swart, Bernhard Steiner, Amanda Welin, Michael Hohl, François Letourneur, Markus A Seeger, Hubert Hilbi
Legionella pneumophila can cause Legionnaires' disease and replicates intracellularly in a distinct Legionella-containing vacuole (LCV). LCV formation is a complex process that involves a plethora of type IV-secreted effector proteins. The effector RidL binds the Vps29 retromer subunit, blocks retrograde vesicle trafficking, and promotes intracellular bacterial replication. Here, we reveal that the 29-kDa N-terminal domain of RidL (RidL2-281) adopts a "foot-like" fold comprising a protruding β-hairpin at its "heel"...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142073/gga1-regulates-signal-dependent-sorting-of-bace1-to-recycling-endosomes-which-moderates-a%C3%AE-production
#2
Wei Hong Toh, Pei Zhi Cheryl Chia, Mohammed Iqbal Hossain, Paul A Gleeson
The diversion of the membrane-bound β-secretase BACE1 from the endo-lysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the SNX4-mediated, signal independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the acidic cluster-dileucine DISLL cytoplasmic tail motif of BACE1...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29135085/retromer-and-the-cimpr-time-for-a-trial-separation
#3
Matthew N J Seaman
The retromer cargo-selective complex (CSC) comprising Vps35, Vps29 and Vps26 mediates the endosome-to-Golgi retrieval of the cation-independent mannose 6-phosphate receptor (CIMPR). Or does it? Recently published data has questioned the validity of this long established theory. Here the evidence for and against a role for the retromer CSC in CIMPR endosome-to-Golgi retrieval is examined in the light of the new data that the SNX-BAR dimer is actually responsible for CIMPR retrieval.
November 14, 2017: Traffic
https://www.readbyqxmd.com/read/29122514/chlamydia-trachomatis-and-its-interaction-with-the-cellular-retromer
#4
REVIEW
Sebastian Banhart, Laura Rose, Lukas Aeberhard, Sophia Koch-Edelmann, Dagmar Heuer
Chlamydia trachomatis is an important human pathogen. This obligate intracellular bacterium grows inside the eukaryotic cell in a membrane-bound compartment, the inclusion. Recent global approaches describe the interactions of C. trachomatis with its host cell and indicate the inclusion is an intracellular trafficking hub embedded into the cellular vesicular trafficking pathways recruiting subunits of the retromer protein complex of the host cell. Here we review these recent developments in deciphering Chlamydia-host cell interactions with emphasis on the role of the retromer complex...
October 26, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29118110/cellular-functions-of-the-autism-risk-factor-ptchd1-in-mice
#5
David Tora, Andrea M Gomez, Jean-Francois Michaud, Patricia T Yam, Frédéric Charron, Peter Scheiffele
The gene PTCHD1 is mutated in patients with autism spectrum disorders (ASD) and intellectual disabilities (ID) and has been hypothesized to contribute to Sonic hedgehog (Shh) signaling and synapse formation. We identify a panel of Ptchd1 interacting proteins that include postsynaptic density proteins and the retromer complex, revealing a link to critical regulators of dendritic and postsynaptic trafficking. Ptchd1 knock-out male mice exhibit cognitive alterations, including defects in a novel object recognition task...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29117568/pten-regulates-glucose-transporter-recycling-by-impairing-snx27-retromer-assembly
#6
Swapnil Rohidas Shinde, Subbareddy Maddika
The tumor suppressor PTEN executes cellular functions predominantly through its phosphatase activity. Here we identified a phosphatase-independent role for PTEN during vesicular trafficking of the glucose transporter GLUT1. PTEN physically interacts with SNX27, a component of the retromer complex that recycles transmembrane receptors such as GLUT1 from endosomes to the plasma membrane. PTEN binding with SNX27 prevents GLUT1 accumulation at the plasma membrane because of defective recycling and thus reduces cellular glucose uptake...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29061884/the-retromer-sorting-nexins-and-the-plant-endomembrane-protein-trafficking
#7
REVIEW
Nicole Heucken, Rumen Ivanov
Protein sorting in the endomembrane system is responsible for the coordination of cellular functions. Plant intracellular trafficking has its own unique features, which include specific regulatory aspects of endosomal sorting and recycling of cargo proteins, mediated by the retromer complex. Recent work has led to significant progress in understanding the role of Arabidopsis retromer subunits in recycling vacuolar sorting receptors and plasma membrane proteins. As a consequence, members of the sorting nexin (SNX) protein family and their interaction partners have emerged as critical protein trafficking regulators, in particular with regard to adaptation to environmental change, such as temperature fluctuations and nutrient deficiency...
October 23, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29061649/retromer-revisited-evolving-roles-for-retromer-in-endosomal-sorting
#8
John P Chamberland, Brigitte Ritter
The highly conserved retromer complex has been linked to cargo retrieval from endosomes to the trans-Golgi network. In this issue, Kvainickas et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201702137) and Simonetti et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201703015) fundamentally question the current retromer model and demonstrate that in mammalian cells, the individual retromer subcomplexes have functionally diverged to organize multiple distinct sorting pathways.
November 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29058661/the-cellular-endosomal-protein-stannin-inhibits-intracellular-trafficking-of-human-papillomavirus-during-virus-entry
#9
Alex Lipovsky, Asu Erden, Eriko Kanaya, Wei Zhang, Mac Crite, Clinton Bradfield, John MacMicking, Daniel DiMaio, John W Schoggins, Akiko Iwasaki
Human papillomaviruses (HPVs) are the most common sexually transmitted viruses and one of the most important infectious causes of cancers worldwide. While prophylactic vaccines are effective against certain strains of HPV, established infections still cause deadly cancers in both men and women. HPV traffics to the nucleus via the retrograde transport pathway, but the mechanism of intracellular transport of non-enveloped viruses such as HPV is incompletely understood. Using an overexpression screen, we identify several genes that control HPV16 entry...
October 23, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29031909/the-retromer-subunit-vps26-mediates-notch-signaling-during-drosophila-oogenesis
#10
Rebecca Starble, Nancy J Pokrywka
During endocytosis, molecules are internalized by the cell through the invagination of the plasma membrane. Endocytosis is required for proper cell function and for normal development in Drosophila. One component of the endocytic pathway is the retromer complex, which recycles transmembrane proteins to other parts of the cell such as the plasma membrane and the trans-Golgi network. Previous studies have shown that mutations to the retromer complex result in developmental defects in Drosophila. In humans, retromer dysfunction has been implicated in Alzheimer's and Parkinson's disease, but little is known about the role of the retromer complex in Drosophila oogenesis...
October 11, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28973312/impaired-axonal-retrograde-trafficking-of-the-retromer-complex-augments-lysosomal-deficits-in-alzheimer-s-disease-neurons
#11
Prasad Tammineni, Yu Young Jeong, Tuancheng Feng, Daniyal Aikal, Qian Cai
Lysosomal proteolysis is essential for the quality control of intracellular components and the maintenance of cellular homeostasis. Lysosomal alterations have been implicated as one of the main cellular defects contributing to the onset and progression of Alzheimer's disease (AD). However, the mechanism underlying lysosomal deficits in AD remains poorly understood. Here, we reveal that lysosomal deficits are attributed to retromer dysfunction induced by altered retromer trafficking in the axon of AD-related mutant human amyloid precursor protein (hAPP) transgenic (Tg) mouse neurons...
November 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28960203/retriever-fetches-integrins-from-endosomes
#12
Catherine Rabouille
Recycling from endosomes to the plasma membrane is an important step in cell homeostasis. The retromer/SNX27/WASH complex recycles numerous receptors, but key ones are still unaccounted for. Now a related conserved heterotrimer, called retriever, has been identified that, together with SNX17, the CCC complex and WASH, mediates the recycling of α5β1 integrins.
September 29, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28954865/retromer-stops-beta-arrestin-1-mediated-signaling-from-internalized-cannabinoid-2-receptors
#13
Carlos Nogueras-Ortiz, Cristina Roman-Vendrell, Gabriel E Mateo-Semidey, Yu-Hsien Liao, Debra A Kendall, Guillermo A Yudowski
G protein-coupled receptors (GPCRs) mediate their complex functions through activation of signaling cascades from receptors localized at the cell surface and endosomal compartments. These signaling pathways are modulated by heterotrimeric G proteins and the scaffold proteins beta-arrestin 1 and 2. However, in contrast to the events occurring at the cell surface, our knowledge of the mechanisms controlling signaling from receptors localized at intracellular compartments is still very limited. Here, we sought to investigate the intracellular signaling from cannabinoid 2 receptor (CB2R)...
September 27, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28950903/bayesian-network-model-for-identification-of-pathways-by-integrating-protein-interaction-with-genetic-interaction-data
#14
Changhe Fu, Su Deng, Guangxu Jin, Xinxin Wang, Zu-Guo Yu
BACKGROUND: Molecular interaction data at proteomic and genetic levels provide physical and functional insights into a molecular biosystem and are helpful for the construction of pathway structures complementarily. Despite advances in inferring biological pathways using genetic interaction data, there still exists weakness in developed models, such as, activity pathway networks (APN), when integrating the data from proteomic and genetic levels. It is necessary to develop new methods to infer pathway structure by both of interaction data...
September 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28935633/sequence-dependent-cargo-recognition-by-snx-bars-mediates-retromer-independent-transport-of-ci-mpr
#15
Boris Simonetti, Chris M Danson, Kate J Heesom, Peter J Cullen
Endosomal recycling of transmembrane proteins requires sequence-dependent recognition of motifs present within their intracellular cytosolic domains. In this study, we have reexamined the role of retromer in the sequence-dependent endosome-to-trans-Golgi network (TGN) transport of the cation-independent mannose 6-phosphate receptor (CI-MPR). Although the knockdown or knockout of retromer does not perturb CI-MPR transport, the targeting of the retromer-linked sorting nexin (SNX)-Bin, Amphiphysin, and Rvs (BAR) proteins leads to a pronounced defect in CI-MPR endosome-to-TGN transport...
November 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28935632/cargo-selective-snx-bar-proteins-mediate-retromer-trimer-independent-retrograde-transport
#16
Arunas Kvainickas, Ana Jimenez-Orgaz, Heike Nägele, Zehan Hu, Jörn Dengjel, Florian Steinberg
The retromer complex, which recycles the cation-independent mannose 6-phosphate receptor (CI-MPR) from endosomes to the trans-Golgi network (TGN), is thought to consist of a cargo-selective VPS26-VPS29-VPS35 trimer and a membrane-deforming subunit of sorting nexin (SNX)-Bin, Amphyphysin, and Rvs (BAR; SNX-BAR) proteins. In this study, we demonstrate that heterodimers of the SNX-BAR proteins, SNX1, SNX2, SNX5, and SNX6, are the cargo-selective elements that mediate the retrograde transport of CI-MPR from endosomes to the TGN independently of the core retromer trimer...
November 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28934248/vps35-deficiency-impairs-slc4a11-trafficking-and-promotes-corneal-dystrophy
#17
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/28933603/autophagy-enables-retromer-dependent-plasma-membrane-translocation-of-slc2a1-glut1-to-enhance-glucose-uptake
#18
Srirupa Roy, Jayanta Debnath
No abstract text is available yet for this article.
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28898487/structural-and-thermodynamic-characterization-of-metal-binding-in-vps29-from-entamoeba-histolytica-implication-in-retromer-function
#19
Vijay Kumar Srivastava, Rupali Yadav, Natsuki Watanabe, Priya Tomar, Madhumita Mukherjee, Samudrala Gourinath, Kumiko Nakada-Tsukui, Tomoyoshi Nozaki, Sunando Datta
Vps29 is the smallest subunit of retromer complex with metallo-phosphatase fold. Although the role of metal in Vps29 is in quest, its metal binding mutants has been reported to affect the localization of the retromer complex in human cells. In this study, we report the structural and thermodynamic consequences of these mutations in Vps29 from the protozoan parasite, Entamoeba histolytica (EhVps29). EhVps29 is a zinc binding protein as revealed by X-ray crystallography and isothermal titration calorimetry. The metal binding pocket of EhVps29 exhibits marked differences in its 3-dimensional architecture and metal coordination in comparison to its human homologs and other metallo-phosphatases...
September 12, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28892079/retriever-is-a-multiprotein-complex-for-retromer-independent-endosomal-cargo-recycling
#20
Kerrie E McNally, Rebecca Faulkner, Florian Steinberg, Matthew Gallon, Rajesh Ghai, David Pim, Paul Langton, Neil Pearson, Chris M Danson, Heike Nägele, Lindsey L Morris, Amika Singla, Brittany L Overlee, Kate J Heesom, Richard Sessions, Lawrence Banks, Brett M Collins, Imre Berger, Daniel D Billadeau, Ezra Burstein, Peter J Cullen
Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multiprotein complex that orchestrates cargo retrieval and recycling and, importantly, is biochemically and functionally distinct from the established retromer pathway. We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer...
October 2017: Nature Cell Biology
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