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Sorting nexin

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https://www.readbyqxmd.com/read/29114050/structure-and-function-of-yeast-atg20-a-sorting-nexin-that-facilitates-autophagy-induction
#1
Hana Popelka, Alejandro Damasio, Jenny E Hinshaw, Daniel J Klionsky, Michael J Ragusa
The Atg20 and Snx4/Atg24 proteins have been identified in a screen for mutants defective in a type of selective macroautophagy/autophagy. Both proteins are connected to the Atg1 kinase complex, which is involved in autophagy initiation, and bind phosphatidylinositol-3-phosphate. Atg20 and Snx4 contain putative BAR domains, suggesting a possible role in membrane deformation, but they have been relatively uncharacterized. Here we demonstrate that, in addition to its function in selective autophagy, Atg20 plays a critical role in the efficient induction of nonselective autophagy...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29109144/autophagic-clearance-of-proteasomes-in-yeast-requires-the-conserved-sorting-nexin-snx4
#2
Antonia A Nemec, Lauren A Howell, Anna K Peterson, Matthew A Murray, Robert J Tomko
Turnover of the 26S proteasome by autophagy is an evolutionarily conserved process that governs cellular proteolytic capacity and eliminates inactive particles. In most organisms, proteasomes are located in both the nucleus and cytoplasm. However, the specific autophagy routes for nuclear and cytoplasmic proteasomes are unclear. Here, we investigate the spatial control of autophagic proteasome turnover in budding yeast (Saccharomyces cerevisiae). We found that nitrogen starvation-induced proteasome autophagy is independent of known nucleophagy pathways, but is compromised when nuclear protein export is blocked...
November 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29080975/loss-of-renal-snx5-results-in-impaired-ide-activity-and-insulin-resistance-in-mice
#3
Fengmin Li, Jian Yang, Van Anthony M Villar, Laureano D Asico, Xiaobo Ma, Ines Armando, Hironobu Sanada, Minoru Yoneda, Robin A Felder, Pedro A Jose, Xiaoyan Wang
AIMS/HYPOTHESIS: We hypothesised that renal sorting nexin 5 (SNX5) regulates the insulin-degrading enzyme (IDE) and, thus, circulating insulin levels. We therefore studied the dynamic interaction between SNX5 and IDE in human renal proximal tubule cells (hRPTCs), as well as in rat and mouse kidneys. METHODS: The regulation of IDE by SNX5 expressed in the kidney was studied in vitro and in vivo. Snx5 or mock siRNA was added to immortalised hRPTCs (passage <20) in culture or selectively infused, via osmotic mini-pump, into the remnant kidney of uninephrectomised mice and rats...
October 28, 2017: Diabetologia
https://www.readbyqxmd.com/read/29080748/overexpression-of-snx7-reduces-a%C3%AE-production-by-enhancing-lysosomal-degradation-of-app
#4
Shaohua Xu, Lu Zhang, Lennart Brodin
Abnormal production of amyloid-β peptides (Aβ) by proteolytic processing of amyloid precursor protein (APP) is thought to be central to the pathogenesis of Alzheimer's disease (AD). Although many efforts have been made to investigate mechanisms that regulate APP processing, many details remain incompletely understood. Sorting nexins (SNXs) are a family of proteins which are involved in many intracellular trafficking events. Several SNXs have been implicated in APP processing and Aβ production. In this study, we extended the investigation to SNX7...
October 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29078380/large-g-protein-%C3%AE-subunit-xl%C3%AE-s-limits-clathrin-mediated-endocytosis-and-regulates-tissue-iron-levels-in-vivo
#5
Qing He, Richard Bouley, Zun Liu, Marc N Wein, Yan Zhu, Jordan M Spatz, Chia-Yu Wang, Paola Divieti Pajevic, Antonius Plagge, Jodie L Babitt, Murat Bastepe
Alterations in the activity/levels of the extralarge G protein α-subunit (XLαs) are implicated in various human disorders, such as perinatal growth retardation. Encoded by GNAS, XLαs is partly identical to the α-subunit of the stimulatory G protein (Gsα), but the cellular actions of XLαs remain poorly defined. Following an initial proteomic screen, we identified sorting nexin-9 (SNX9) and dynamins, key components of clathrin-mediated endocytosis, as binding partners of XLαs. Overexpression of XLαs in HEK293 cells inhibited internalization of transferrin, a process that depends on clathrin-mediated endocytosis, while its ablation by CRISPR/Cas9 in an osteocyte-like cell line (Ocy454) enhanced it...
October 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29061884/the-retromer-sorting-nexins-and-the-plant-endomembrane-protein-trafficking
#6
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/29034896/generation-of-induced-pluripotent-stem-cells-aro-ipsc1-11-from-a-patient-with-autosomal-recessive-osteopetrosis-harboring-the-c-212-1g-t-mutation-in-snx10-gene
#7
Maojia Xu, Eva-Lena Stattin, Mary Murphy, Frank Barry
Pathogenic sequence variants in the Sorting Nexin 10 (SNX10) gene have been associated with autosomal recessive osteopetrosis (ARO) in human. In this study, an induced pluripotent stem cell (iPSC) line (ARO-iPSC1-11) was generated from an ARO patient carrying the homozygous c.212+1G>T mutation in SNX10, using a retroviral-based reprogramming protocol. Characterization confirmed that the generated iPSCs expressed pluripotency markers, displayed normal karyotype, showed pluripotent differentiation capacity and retained the targeted mutation...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28935633/sequence-dependent-cargo-recognition-by-snx-bars-mediates-retromer-independent-transport-of-ci-mpr
#8
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
#9
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/28903313/snx10-promotes-phagosome-maturation-in-macrophages-and-protects-mice-against-listeria-monocytogenes-infection
#10
Jun Lou, Xiawei Li, Wei Huang, Jingjing Liang, Mingzhu Zheng, Ting Xu, Jun Lyu, Dan Li, Qin Xu, Xuexiao Jin, Guotong Fu, Di Wang, Linrong Lu
Listeria monocytogenes (L. monocytogenes), which is a facultative intracellular bacterial pathogen that causes listeriosis, is widely used to study the mammalian immune response to infection. After phagocytosis by professional phagocytes, L. monocytogenes is initially contained within phagosomes, which mature into phagolysosomes, where the bacteria are degraded. Although phagocytosis and subsequent phagosome maturation is essential for the clearance of infectious microbial pathogens, the underlying regulatory mechanisms are still unclear...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28892079/retriever-is-a-multiprotein-complex-for-retromer-independent-endosomal-cargo-recycling
#11
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
https://www.readbyqxmd.com/read/28836715/sorting-nexin-movps17-is-required-for-fungal-development-and-plant-infection-by-regulating-endosome-dynamics-in-the-rice-blast-fungus
#12
Huawei Zheng, Zhongkun Guo, Yang Xi, Mingyue Yuan, Yahong Lin, Congxian Wu, Yakubu Saddeeq Abubakar, Xianying Dou, Guangpu Li, Zonghua Wang, Wenhui Zheng, Jie Zhou
Vps17 is a sorting nexin (SNX) and a component of the retromer, a protein complex mediating retrograde vesicle transport between endosomes and the trans-Golgi network. However, its role in the development and pathogenicity of filamentous fungi such as the rice blast fungus (Magnaporthe oryzae) remains unclear. We investigate the functional relationship between the SNX and the cargo-selective complex (CSC) of the fungal retromer by genetic analysis, live cell imaging and immunological assay. Our data show that the MoVps17 null mutation causes defects in growth, development and pathogenicity in M...
August 24, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28778068/snx10-promotes-phagosome-maturation-in-macrophages-and-protects-mice-against-listeria-monocytogenes-infection
#13
Jun Lou, Xiawei Li, Wei Huang, Jingjing Liang, Mingzhu Zheng, Ting Xu, Jun Lyu, Dan Li, Qin Xu, Xuexiao Jin, Guotong Fu, Di Wang, Linrong Lu
Listeria monocytogenes (L. monocytogenes),which is a facultative intracellular bacterial pathogen that causes listeriosis, is widely used to study the mammalian immune response to infection. After phagocytosis by professional phagocytes, L. monocytogenes is initially contained within phagosomes, which mature into phagolysosomes, where the bacteria are degraded. Although phagocytosis and subsequent phagosome maturation is essential for the clearance of infectious microbial pathogens, the underlying regulatory mechanisms are still unclear...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28771744/loss-of-sorting-nexin-5-stabilizes-internalized-growth-factor-receptors-to-promote-thyroid-cancer-progression
#14
Sumito Jitsukawa, Ryuta Kamekura, Koji Kawata, Fumie Ito, Akinori Sato, Hiroshi Matsumiya, Tomonori Nagaya, Keiji Yamashita, Terufumi Kubo, Tomoki Kikuchi, Noriyuki Sato, Tadashi Hasegawa, Hiroshi Kiyonari, Yoshiko Mukumoto, Ken-Ichi Takano, Tetsuo Himi, Shingo Ichimiya
Thyroid carcinoma is the most common endocrine malignancy and its prevalence has recently been increasing worldwide. We previously reported that the level of sorting nexin 5 (Snx5), an endosomal translocator, is preferentially decreased during the progression of well-differentiated thyroid carcinoma into poorly differentiated carcinoma. To address the functional role of Snx5 in the development and progression of thyroid carcinoma, we established Snx5-deficient (Snx5(-/-) ) mice. In comparison to wild-type (Snx5(+/+) ) mice, Snx5(-/-) mice showed enlarged thyroid glands that consisted of thyrocytes with large irregular-shaped vacuoles...
November 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28757549/updated-insight-into-the-physiological-and-pathological-roles-of-the-retromer-complex
#15
REVIEW
Yakubu Saddeeq Abubakar, Wenhui Zheng, Stefan Olsson, Jie Zhou
Retromer complexes mediate protein trafficking from the endosomes to the trans-Golgi network (TGN) or through direct recycling to the plasma membrane. In yeast, they consist of a conserved trimer of the cargo selective complex (CSC), Vps26-Vps35-Vps29 and a dimer of sorting nexins (SNXs), Vps5-Vps17. In mammals, the CSC interacts with different kinds of SNX proteins in addition to the mammalian homologues of Vps5 and Vps17, which further diversifies retromer functions. The retromer complex plays important roles in many cellular processes including restriction of invading pathogens...
July 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28712807/snx16-regulates-the-recycling-of-e-cadherin-through-a-unique-mechanism-of-coordinated-membrane-and-cargo-binding
#16
Jinxin Xu, Leilei Zhang, Yinghua Ye, Yongli Shan, Chanjuan Wan, Junfeng Wang, Duanqing Pei, Xiaodong Shu, Jinsong Liu
E-Cadherin is a major component of adherens junctions on cell surfaces. SNX16 is a unique member of sorting nexins that contains a coiled-coil (CC) domain downstream of the PX domain. We report here that SNX16 regulates the recycling trafficking of E-cadherin. We solved the crystal structure of PX-CC unit of SNX16 and revealed a unique shear shaped homodimer. We identified a novel PI3P binding pocket in SNX16 that consists of both the PX and the CC domains. Surprisingly, we showed that the PPII/α2 loop, which is generally regarded as a membrane insertion loop in PX family proteins, is involved in the E-cadherin binding with SNX16...
August 1, 2017: Structure
https://www.readbyqxmd.com/read/28664153/sopb-mediated-recruitment-of-snx18-facilitates-salmonella-typhimurium-internalization-by-the-host-cell
#17
David Liebl, Xiaying Qi, Yang Zhe, Timothy C Barnett, Rohan D Teasdale
To invade epithelial cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) induces macropinocytosis through the action of virulence proteins delivered across the host cell membrane via a type III secretion system. We show that after docking at the plasma membrane S. Typhimurium triggers rapid recruitment of cytosolic SNX18, a SH3-PX-BAR domain sorting nexin protein, to the bacteria-induced membrane ruffles and to the nascent Salmonella-containing vacuole. SNX18 recruitment required the inositol-phosphatase activity of the Salmonella effector SopB and an intact phosphoinositide-binding site within the PX domain of SNX18, but occurred independently of Rho-GTPases Rac1 and Cdc42 activation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28620080/the-sorting-nexin-3-retromer-pathway-regulates-the-cell-surface-localization-and-activity-of-a-wnt-activated-polycystin-channel-complex
#18
Shuang Feng, Andrew J Streets, Vasyl Nesin, Uyen Tran, Hongguang Nie, Marta Onopiuk, Oliver Wessely, Leonidas Tsiokas, Albert C M Ong
Autosomal dominant polycystic kidney disease (ADPKD) is caused by inactivating mutations in PKD1 (85%) or PKD2 (15%). The ADPKD proteins encoded by these genes, polycystin-1 (PC1) and polycystin-2 (PC2), form a plasma membrane receptor-ion channel complex. However, the mechanisms controlling the subcellular localization of PC1 and PC2 are poorly understood. Here, we investigated the involvement of the retromer complex, an ancient protein module initially discovered in yeast that regulates the retrieval, sorting, and retrograde transport of membrane receptors...
October 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28618099/epec-effector-espf-promotes-crumbs3-endocytosis-and-disrupts-epithelial-cell-polarity
#19
Rocio Tapia, Sarah E Kralicek, Gail A Hecht
Enteropathogenic Escherichia coli (EPEC) uses a type III secretion system to inject effector proteins into host intestinal epithelial cells causing diarrhoea. EPEC infection redistributes basolateral proteins β1-integrin and Na(+) /K(+) ATPase to the apical membrane of host cells. The Crumbs (Crb) polarity complex (Crb3/Pals1/Patj) is essential for epithelial cell polarisation and tight junction (TJ) assembly. Here, we demonstrate that EPEC displaces Crb3 and Pals1 from the apical membrane to the cytoplasm of cultured intestinal epithelial cells and colonocytes of infected mice...
November 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28592808/snx10-gene-mutation-leading-to-osteopetrosis-with-dysfunctional-osteoclasts
#20
Eva-Lena Stattin, Petra Henning, Joakim Klar, Emma McDermott, Christina Stecksen-Blicks, Per-Erik Sandström, Therese G Kellgren, Patrik Rydén, Göran Hallmans, Torsten Lönnerholm, Adam Ameur, Miep H Helfrich, Fraser P Coxon, Niklas Dahl, Johan Wikström, Ulf H Lerner
Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Västerbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Tonsillar herniation, foramen magnum stenosis, and severe osteomyelitis of the jaw were common clinical features...
June 7, 2017: Scientific Reports
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