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https://www.readbyqxmd.com/read/28053230/snx-1-and-rme-8-oppose-the-assembly-of-hgrs-1-escrt-0-degradative-microdomains-on-endosomes
#1
Anne Norris, Prasad Tammineni, Simon Wang, Julianne Gerdes, Alexandra Murr, Kelvin Y Kwan, Qian Cai, Barth D Grant
After endocytosis, transmembrane cargo reaches endosomes, where it encounters complexes dedicated to opposing functions: recycling and degradation. Microdomains containing endosomal sorting complexes required for transport (ESCRT)-0 component Hrs [hepatocyte growth factor-regulated tyrosine kinase substrate (HGRS-1) in Caenorhabditis elegans] mediate cargo degradation, concentrating ubiquitinated cargo and organizing the activities of ESCRT. At the same time, retromer associated sorting nexin one (SNX-1) and its binding partner, J-domain protein RME-8, sort cargo away from degradation, promoting cargo recycling to the Golgi...
January 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28040727/a-conserved-retromer-sorting-motif-is-essential-for-mitochondrial-dlp1-recycling-by-vps35-in-parkinson-s-disease-model
#2
Wenzhang Wang, Xiaopin Ma, Leping Zhou, Jun Liu, Xiongwei Zhu
Impaired mitochondria dynamics and quality control are involved in mitochondrial dysfunction and pathogenesis of Parkinson's disease (PD). VPS35 mutations cause autosomal dominant PD and we recently demonstrated that fPD-associated VPS35 mutants can cause mitochondrial fragmentation through enhanced VPS35-DLP1 interaction. In this study, we focused on the specific sites on DLP1 responsible for the VPS35-DLP1 interaction. A highly conserved FLV motif was identified in the C-terminus of DLP1, mutation of which significantly reduced VPS35-DLP1 interaction...
December 30, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28026081/distinct-complexes-of-yeast-snx4-family-snx-bars-mediate-retrograde-trafficking-of-snc1-and-atg27
#3
Mengxiao Ma, Christopher G Burd, Richard J Chi
The yeast SNX4 sub-family of sorting nexin containing a Bin-Amphiphysin-Rvs domain (SNX-BAR) proteins, Snx4/Atg24, Snx41 and Atg20/Snx42, are required for endocytic recycling and selective autophagy. Here, we show that Snx4 forms 2 functionally distinct heterodimers: Snx4-Atg20 and Snx4-Snx41. Each heterodimer coats an endosome-derived tubule that mediates retrograde sorting of distinct cargo; the v-SNARE, Snc1, is a cargo of the Snx4-Atg20 pathway, and Snx4-Snx41 mediates retrograde sorting of Atg27, an integral membrane protein implicated in selective autophagy...
December 27, 2016: Traffic
https://www.readbyqxmd.com/read/27984059/cruising-the-cellular-highways-how-human-papillomavirus-travels-from-the-surface-to-the-nucleus
#4
REVIEW
Stephen DiGiuseppe, Malgorzata Bienkowska-Haba, Lucile G Guion, Martin Sapp
The non-enveloped human papillomaviruses (HPVs) specifically target epithelial cells of the skin and mucosa. Successful infection requires a lesion in the stratified tissue for access to the basal cells. Herein, we discuss our recent progress in understanding binding, internalization, uncoating, and intracellular trafficking of HPV particles. Our focus will be on HPV type 16, which is the most common HPV type associated with various anogenital and oropharyngeal carcinomas. The study of HPV entry has revealed a number of novel cellular pathways utilized during infection...
October 28, 2016: Virus Research
https://www.readbyqxmd.com/read/27964832/role-of-the-vps35-d620n-mutation-in-parkinson-s-disease
#5
REVIEW
Megha Mohan, George D Mellick
Parkinson's disease (PD) is a neurodegenerative disorder involving the loss of dopaminergic neurons in the brain. Following the discovery of the PD-causing D620N mutation in the VPS35 (Vacuolar sorting protein 35) gene, dysfunction in the subcellular retromer complex has been strongly implicated in pathogenesis of PD. Although the function and dysfunction of the retromer has been a focus of study for some time, the role of this complex in the development of PD is not fully understood. Investigating cellular alterations that occur when the retromer is rendered dysfunctional, such as when the D620N disease-causing mutation is introduced into various model systems, shows that endosomal processing defects are major contributors to the disease phenotype...
December 5, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27942972/the-influenza-a-virus-matrix-protein-2-undergoes-retrograde-transport-from-the-endoplasmic-reticulum-into-the-cytoplasm-and-bypasses-cytoplasmic-proteasomal-degradation
#6
Sanchari Bhowmick, Chandrani Chakravarty, Shanmugaapriya Sellathamby, Sunil K Lal
The matrix protein 2 (M2) is a spliced product of segment 7 genome of influenza A virus. Previous studies indicate its role in uncoating of the viral ribonucleoprotein complex during viral entry and in membrane scission while budding. Despite its crucial role in the viral life cycle, little is known about its subcellular distribution and dynamics. In this study, we have shown that the M2 protein is translocated from the membrane to the cytoplasm by a retrograde route via endosomes and the Golgi network. It utilizes retromer cargo while moving from the endosome to the trans-Golgi network and prevents endosome fusion with the lysosome...
December 9, 2016: Archives of Virology
https://www.readbyqxmd.com/read/27932943/vacuolar-protein-sorting-genes-in-parkinson-s-disease-a-re-appraisal-of-mutations-detection-rate-and-neurobiology-of-disease
#7
REVIEW
Stefano Gambardella, Francesca Biagioni, Rosangela Ferese, Carla L Busceti, Alessandro Frati, Giuseppe Novelli, Stefano Ruggieri, Francesco Fornai
Mammalian retromers play a critical role in protein trans-membrane sorting from endosome to the trans-Golgi network (TGN). Recently, retromer alterations have been related to the onset of Parkinson's Disease (PD) since the variant p.Asp620Asn in VPS35 (Vacuolar Protein Sorting 35) was identified as a cause of late onset PD. This variant causes a primary defect in endosomal trafficking and retromers formation. Other mutations in VPS genes have been reported in both sporadic and familial PD. These mutations are less defined...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27929418/yeast-reporter-assay-to-identify-cellular-components-of-ricin-toxin-a-chain-trafficking
#8
Björn Becker, Tina Schnöder, Manfred J Schmitt
RTA, the catalytic A-subunit of the ribosome inactivating A/B toxin ricin, inhibits eukaryotic protein biosynthesis by depurination of 28S rRNA. Although cell surface binding of ricin holotoxin is mainly mediated through its B-subunit (RTB), sole application of RTA is also toxic, albeit to a significantly lower extent, suggesting alternative pathways for toxin uptake and transport. Since ricin toxin trafficking in mammalian cells is still not fully understood, we developed a GFP-based reporter assay in yeast that allows rapid identification of cellular components required for RTA uptake and subsequent transport through a target cell...
December 6, 2016: Toxins
https://www.readbyqxmd.com/read/27924069/retrograde-trafficking-of-vmat2-and-its-role-in-protein-stability-in-non-neuronal-cells
#9
Qiuzi Wu, Hongfei Xu, Wei Wang, Fei Chang, Yu Jiang, Yongjian Liu
Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2 (VMAT2) contributes to the pathogenesis of Parkinson's disease. That has been linked to aberrant subcellular retrograde trafficking as strongly indicated by recent genomic studies on familial Parkinson's diseases. However, whether VMAT2 function is regulated by retrograde trafficking is unknown. By using biochemistry and cell biology approaches, we have shown that VMAT2 was stringently localized to the trans-Golgi network and underwent retrograde trafficking in non-neuronal cells...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27917878/spatiotemporal-control-of-interferon-induced-jak-stat-signalling-and-gene-transcription-by-the-retromer-complex
#10
Daniela Chmiest, Nanaocha Sharma, Natacha Zanin, Christine Viaris de Lesegno, Massiullah Shafaq-Zadah, Vonick Sibut, Florent Dingli, Philippe Hupé, Stephan Wilmes, Jacob Piehler, Damarys Loew, Ludger Johannes, Gideon Schreiber, Christophe Lamaze
Type-I interferons (IFNs) play a key role in the immune defences against viral and bacterial infections, and in cancer immunosurveillance. We have established that clathrin-dependent endocytosis of the type-I interferon (IFN-α/β) receptor (IFNAR) is required for JAK/STAT signalling. Here we show that the internalized IFNAR1 and IFNAR2 subunits of the IFNAR complex are differentially sorted by the retromer at the early endosome. Binding of the retromer VPS35 subunit to IFNAR2 results in IFNAR2 recycling to the plasma membrane, whereas IFNAR1 is sorted to the lysosome for degradation...
December 5, 2016: Nature Communications
https://www.readbyqxmd.com/read/27912055/retromer-sets-a-trap-for-endosomal-cargo-sorting
#11
Ludger Johannes, Christian Wunder
Membrane trafficking from endosomes to the trans-Golgi network or the plasma membrane is driven by the retromer complex. Through structural analysis of the cargo-bound complex, Lucas et al. describe a mechanism by which endosomal membrane recruitment and cargo recognition are integrated through cooperative interactions between retromer subunits.
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27909246/retromer-wash-dependent-sorting-of-nutrient-transporters-requires-a-multivalent-interaction-network-with-ankrd50
#12
Arunas Kvainickas, Ana Jimenez Orgaz, Heike Nägele, Britta Diedrich, Kate J Heesom, Jörn Dengjel, Peter J Cullen, Florian Steinberg
Retromer and the associated actin polymerizing WASH-complex are essential for the endocytic recycling of a wide range of integral membrane proteins. A hereditary Parkinson's disease causing point mutation (D620N) in the retromer subunit VPS35 perturbs retromer's association with the WASH-complex and also with the uncharacterized protein Ankyrin Repeat Domain Containing Protein 50 (ANKRD50). Here, we firmly establish ANKRD50 as a novel and essential component of the SNX27-retromer-WASH supercomplex. Depletion of ANKRD50 in HeLa or U2OS cells phenocopied the loss of endosome to cell surface recycling of multiple transmembrane proteins seen upon suppression of SNX27, retromer or WASH-complex components...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27894086/the-anti-tumor-drug-2-hydroxyoleic-acid-minerval-stimulates-signaling-and-retrograde-transport
#13
Maria L Torgersen, Tove Irene Klokk, Simona Kavaliauskiene, Christian Klose, Kai Simons, Tore Skotland, Kirsten Sandvig
2-hydroxyoleic acid (OHOA, Minerval®) is an example of a substance used for membrane lipid therapy, where the cellular membranes rather than specific proteins constitute the therapeutical target. OHOA is thought to mediate its anti-tumor effect by affecting the biophysical properties of membranes, which leads to altered recruitment and activation of amphitropic proteins, altered cellular signaling, and eventual cell death. Little is known about the initial signaling events upon treatment with OHOA, and whether the altered membrane properties would have any impact on the dynamic intracellular transport system...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889239/structural-mechanism-for-cargo-recognition-by-the-retromer-complex
#14
María Lucas, David C Gershlick, Ander Vidaurrazaga, Adriana L Rojas, Juan S Bonifacino, Aitor Hierro
Retromer is a multi-protein complex that recycles transmembrane cargo from endosomes to the trans-Golgi network and the plasma membrane. Defects in retromer impair various cellular processes and underlie some forms of Alzheimer's disease and Parkinson's disease. Although retromer was discovered over 15 years ago, the mechanisms for cargo recognition and recruitment to endosomes have remained elusive. Here, we present an X-ray crystallographic analysis of a four-component complex comprising the VPS26 and VPS35 subunits of retromer, the sorting nexin SNX3, and a recycling signal from the divalent cation transporter DMT1-II...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27889227/gpcr-signaling-and-trafficking-the-long-and-short-of-it
#15
REVIEW
Nathan J Pavlos, Peter A Friedman
Emerging findings disclose unexpected components of G protein-coupled receptor (GPCR) signaling and cell biology. Select GPCRs exhibit classical signaling, that is restricted to cell membranes, as well as newly described persistent signaling that depends on internalization of the GPCR bound to β-arrestins. Termination of non-canonical endosomal signaling requires intraluminal acidification and sophisticated protein trafficking machineries. Recent studies reveal the structural determinants of the trafficking chaperones...
November 23, 2016: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/27883263/cargo-selectivity-of-yeast-sorting-nexins
#16
Björn D M Bean, Michael Davey, Elizabeth Conibear
Sorting nexins are PX domain-containing proteins that bind phospholipids and often act in membrane trafficking where they help to select cargo. However, the functions and cargo specificities of many sorting nexins are unknown. Here, a high-throughput imaging screen was used to identify new sorting nexin cargo in the yeast Saccharomyces cerevisiae. Deletions of nine different sorting nexins were screened for mislocalization of a set of GFP-tagged membrane proteins found at the plasma membrane, Golgi or endosomes...
November 24, 2016: Traffic
https://www.readbyqxmd.com/read/27872751/novel-gene-tmem230-linked-to-parkinson-s-disease
#17
EDITORIAL
Diana A Olszewska, Conor Fearon, Tim Lynch
Mutations in six genes are known to cause Parkinson's disease (PD) (autosomal dominant: alpha-synuclein, LRRK2, VPS35 and autosomal recessive: Parkin, PINK1 and DJ1) and number of other genes are implicated. In a recent article Deng and colleagues studied a large four generation American family of European descent and linked mutations in a novel gene, transmembrane-protein 230 gene (TMEM230) with lewy body confirmed PD. The authors demonstrated that pathogenic TMEM230 variants in primary mouse neurons affected movement of synaptic vesicles suggesting that TMEM230 may slow vesicular transport...
2016: Journal of Clinical Movement Disorders
https://www.readbyqxmd.com/read/27848911/phospholipase-d-activity-couples-plasma-membrane-endocytosis-with-retromer-dependent-recycling
#18
Rajan Thakur, Aniruddha Panda, Elise Coessens, Nikita Raj, Shweta Yadav, Sruthi Balakrishnan, Qifeng Zhang, Plamen Georgiev, Bishal Basak, Renu Pasricha, Michael Jo Wakelam, Nicholas T Ktistakis, Padinjat Raghu
During illumination, the light-sensitive plasma membrane (rhabdomere) of Drosophila photoreceptors undergoes turnover with consequent changes in size and composition. However, the mechanism by which illumination is coupled to rhabdomere turnover remains unclear. We find that photoreceptors contain a light-dependent phospholipase D (PLD) activity. During illumination, loss of PLD resulted in an enhanced reduction in rhabdomere size, accumulation of Rab7 positive, rhodopsin1-containing vesicles (RLVs) in the cell body and reduced rhodopsin protein...
November 16, 2016: ELife
https://www.readbyqxmd.com/read/27827364/structural-and-mechanistic-insights-into-regulation-of-the-retromer-coat-by-tbc1d5
#19
Da Jia, Jin-San Zhang, Fang Li, Jing Wang, Zhihui Deng, Mark A White, Douglas G Osborne, Christine Phillips-Krawczak, Timothy S Gomez, Haiying Li, Amika Singla, Ezra Burstein, Daniel D Billadeau, Michael K Rosen
Retromer is a membrane coat complex that is recruited to endosomes by the small GTPase Rab7 and sorting nexin 3. The timing of this interaction and consequent endosomal dynamics are thought to be regulated by the guanine nucleotide cycle of Rab7. Here we demonstrate that TBC1d5, a GTPase-activating protein (GAP) for Rab7, is a high-affinity ligand of the retromer cargo selective complex VPS26/VPS29/VPS35. The crystal structure of the TBC1d5 GAP domain bound to VPS29 and complementary biochemical and cellular data show that a loop from TBC1d5 binds to a conserved hydrophobic pocket on VPS29 opposite the VPS29-VPS35 interface...
November 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27816670/two-barcodes-encoded-by-the-type-1-pdz-and-by-phospho-ser-312-regulate-retromer-wash-mediated-sorting-of-the-%C3%A3-1-adrenergic-receptor-from-endosomes-to-the-plasma-membrane
#20
Mohammed M Nooh, Suleiman W Bahouth
Recycling of the majority of agonist-internalized GPCR is dependent on a type I-PDZ "barcode" in their C-tail. The recycling of wild-type (WT) ß1-AR is also dependent on its default "type-1 PDZ barcode", but trafficking of the ß1-AR is inhibited when PKA or its substrate serine at position 312 (Ser(312)) are inactivated. We tested the hypothesis that phospho-Ser(312) provided a second barcode for ß1-AR sorting from endosomes to the plasma membrane by determining the role of retromer/WASH complexes in ß1-AR trafficking...
January 2017: Cellular Signalling
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