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https://www.readbyqxmd.com/read/28214893/the-role-of-netrins-and-their-receptors-in-epithelial-mesenchymal-plasticity-during-development
#1
Michael J Murray
Transitions between mesenchymal and epithelial cells are underpinned by changes in motility, adhesion, and polarity. Netrins and their receptors can control each of these cellular properties, and are emerging as important regulators of epithelial mesenchymal plasticity (EMP). Netrins were first identified in the worm Caenorhabditis elegans as secreted chemoattractants/repellents that could guide migrating mesodermal cells and axonal growth cones. Orthologues were subsequently found to play conserved roles in vertebrates and in the vinegar fly Drosophila...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28202721/distinct-c-mannosylation-of-netrin-receptor-thrombospondin-type-1-repeats-by-mammalian-dpy19l1-and-dpy19l3
#2
Aleksandra Shcherbakova, Birgit Tiemann, Falk F R Buettner, Hans Bakker
Thrombospondin type 1 repeats (TSRs) occur in diverse proteins involved in adhesion and signaling. The two extracellular TSRs of the netrin receptor UNC5A contain WxxWxxWxxC motifs that can be C-mannosylated on all tryptophans. A single C-mannosyltransferase (dumpy-19, DPY-19), modifying the first two tryptophans, occurs in Caenorhabditis elegans, but four putative enzymes (DPY-19-like 1-4, DPY19L1-4) exist in mammals. Single and triple CRISPR-Cas9 knockouts of the three homologs that are expressed in Chinese hamster ovary cells (DPY19L1, DPY19L3, and DPY19L4) and complementation experiments with mouse homologs showed that DPY19L1 preferentially mannosylates the first two tryptophans and DPY19L3 prefers the third, whereas DPY19L4 has no function in TSR glycosylation...
February 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28196860/the-nclx-type-na-ca-2-exchanger-ncx-9-is-required-for-patterning-of-neural-circuits-in-caenorhabditis-elegans
#3
Vishal Sharma, Soumitra Roy, Israel Sekler, Damien M O'Halloran
NCLX is a Na(+)/Ca(2+) exchanger that uses energy stored in the transmembrane sodium gradient to facilitate the exchange of sodium ions for ionic calcium. Mammals have a single NCLX, which has been shown to function primarily at the mitochondrion and is an important regulator of neuronal physiology by contributing to neurotransmission and synaptic plasticity. The role of NCLX in developmental cell patterning, for example, in neural circuits, is largely unknown. Here we describe a novel role for the Caenorhabditis elegans NCLX-type protein, NCX-9, in neural circuit formation...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28186165/netrin-1-improves-functional-recovery-through-autophagy-regulation-by-activating-the-ampk-mtor-signaling-pathway-in-rats-with-spinal-cord-injury
#4
Liangjie Bai, Xifan Mei, Zhaoliang Shen, Yunlong Bi, Yajiang Yuan, Zhanpeng Guo, Hongyu Wang, Haosen Zhao, Zipeng Zhou, Chen Wang, Kunming Zhu, Gang Li, Gang Lv
Autophagy is an process for the degradation of cytoplasmic aggregated proteins and damaged organelles and plays an important role in the development of SCI. In this study, we investigated the therapeutic effect of Netrin-1 and its potential mechanism for autophagy regulation after SCI. A rat model of SCI was established and used for analysis. Results showed that administration of Netrin-1 not only significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK) but also reduced the phosphorylation of mammalian target of rapamycin (mTOR) and P70S6K...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174720/netrin-1-protects-hepatocytes-against-cell-death-through-sustained-translation-during-the-unfolded-protein-response
#5
Thomas Lahlali, Marie-Laure Plissonnier, Cristina Romero-López, Maud Michelet, Benjamin Ducarouge, Alfredo Berzal-Herranz, Fabien Zoulim, Patrick Mehlen, Romain Parent
BACKGROUND & AIMS: Netrin-1, a multifunctional secreted protein, is up-regulated in cancer and inflammation. Netrin-1 blocks apoptosis induced by the prototypical dependence receptors deleted in colorectal carcinoma and uncoordinated phenotype-5. Although the unfolded protein response (UPR) triggers apoptosis on exposure to stress, it first attempts to restore endoplasmic reticulum homeostasis to foster cell survival. Importantly, UPR is implicated in chronic liver conditions including hepatic oncogenesis...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174715/netrin-1-needed-help-for-throughput-in-the-er-in-patients-with%C3%A2-liver-disease
#6
EDITORIAL
Seth J Karp
No abstract text is available yet for this article.
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28114100/the-genetics-of-axon-guidance-and-axon-regeneration-in-caenorhabditis-elegans
#7
Andrew D Chisholm, Harald Hutter, Yishi Jin, William G Wadsworth
The correct wiring of neuronal circuits depends on outgrowth and guidance of neuronal processes during development. In the past two decades, great progress has been made in understanding the molecular basis of axon outgrowth and guidance. Genetic analysis in Caenorhabditis elegans has played a key role in elucidating conserved pathways regulating axon guidance, including Netrin signaling, the slit Slit/Robo pathway, Wnt signaling, and others. Axon guidance factors were first identified by screens for mutations affecting animal behavior, and by direct visual screens for axon guidance defects...
November 2016: Genetics
https://www.readbyqxmd.com/read/28108253/dcc-haploinsufficiency-regulates-dopamine-receptor-expression-across-postnatal-lifespan
#8
Matthew Pokinko, Alanna Grant, Florence Shahabi, Yvan Dumont, Colleen Manitt, Cecilia Flores
Adolescence is a period during which the medial prefrontal cortex (mPFC) undergoes significant remodeling. The netrin-1 receptor, deleted in colorectal cancer (DCC), controls the extent and organization of mPFC dopamine connectivity during adolescence and in turn directs mPFC functional and structural maturation. Dcc haploinsufficiency leads to increased mPFC dopamine input, which causes improved cognitive processing and resilience to behavioral effects of stimulant drugs of abuse. Here we examine the effects of Dcc haploinsufficiency on the dynamic expression of dopamine receptors in forebrain targets of C57BL6 mice...
January 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28089174/neonatal-acute-kidney-injury-severity-and-recovery-prediction-and-the-role-of-serum-and-urinary-biomarkers
#9
Deirdre U Sweetman
Neonatal acute kidney injury is common, in part due to incomplete renal maturation and also due to frequent exposure to risk factors for acute kidney injury such as perinatal asphyxia, extracorporeal-membrane-oxygenation, cardiac surgery, sepsis, prematurity and nephrotoxicity. However the current method by which acute kidney injury is diagnosed is sub-optimal and not universally accepted which impairs the accurate estimation of the true incidence of neonatal acute kidney injury. Serum Cystatin-C, urinary NGAL, KIM-1 and IL-18 are promising neonatal acute kidney injury biomarkers however the diagnosis of acute kidney injury remains serum creatinine/urine output-based in many studies...
January 11, 2017: Early Human Development
https://www.readbyqxmd.com/read/28074533/netrin-g1-its-downregulation-in-the-nucleus-accumbens-of-cocaine-conditioned-mice-and-genetic-association-in-human-cocaine-dependence
#10
Sabah Kelaï, Nicolas Ramoz, Jean-Marie Moalic, Florence Noble, Naguib Mechawar, Sandrine Imbeaud, Gustavo Turecki, Michel Simonneau, Philip Gorwood, Gilles Maussion
Netrin G1 is a presynaptic ligand involved in axonal projection. Although molecular mechanisms underlying cocaine addiction are still poorly understood, Netrin G1 might have a role as a regulator of anxiety, fear and spatial memory, behavioural traits impaired in the context of cocaine exposure. In this study, the Netrin G1 (Ntng1) expression was investigated in the nucleus accumbens of mice primarily conditioned to cocaine using a place preference paradigm. A genetic association study was then conducted on 146 multiplex families of the Collaborative study on Genetics of Alcoholism, in which seven single nucleotide polymorphisms located in the NTNG1 gene were genotyped...
January 11, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28069038/motility-of-glioblastoma-cells-is-driven-by-netrin-1-induced-gain-of-stemness
#11
Irene Ylivinkka, Harri Sihto, Olli Tynninen, Yizhou Hu, Aki Laakso, Riku Kivisaari, Pirjo Laakkonen, Jorma Keski-Oja, Marko Hyytiäinen
BACKGROUND: Glioblastoma is an untreatable brain cancer. The tumors contain a population of stem-like cells which are highly invasive and resistant to therapies. These cells are the main reason for the lethality of glioblastoma. Extracellular guidance molecule netrin-1 promotes the invasiveness and survival of various cancer cell types. We have previously found that netrin-1 activates Notch signaling, and Notch signaling associates with cell stemness. Therefore, we have here investigated the effects of netrin-1 on glioblastoma pathogenesis and glioblastoma cell stemness...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28057929/a-novel-role-for-the-dna-repair-gene-rad51-in-netrin-1-signalling
#12
K A Glendining, D Markie, R J M Gardner, E A Franz, S P Robertson, C L Jasoni
Mutations in RAD51 have recently been linked to human Congenital Mirror Movements (CMM), a developmental disorder of the motor system. The only gene previously linked to CMM encodes the Netrin-1 receptor DCC, which is important for formation of corticospinal and callosal axon tracts. Thus, we hypothesised that Rad51 has a novel role in Netrin-1-mediated axon development. In mouse primary motor cortex neurons, Rad51 protein was redistributed distally down the axon in response to Netrin-1, further suggesting a functional link between the two...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052247/sema-1a-reverse-signaling-promotes-midline-crossing-in-response-to-secreted-semaphorins
#13
Melissa Hernandez-Fleming, Ethan W Rohrbach, Greg J Bashaw
Commissural axons must cross the midline to form functional midline circuits. In the invertebrate nerve cord and vertebrate spinal cord, midline crossing is mediated in part by Netrin-dependent chemoattraction. Loss of crossing, however, is incomplete in mutants for Netrin or its receptor Frazzled/DCC, suggesting the existence of additional pathways. We identified the transmembrane Semaphorin, Sema-1a, as an important regulator of midline crossing in the Drosophila CNS. We show that in response to the secreted Semaphorins Sema-2a and Sema-2b, Sema-1a functions as a receptor to promote crossing independently of Netrin...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28038459/the-netrin-4-neogenin-1-axis-promotes-neuroblastoma-cell-survival-and-migration
#14
Andrea A Villanueva, Paulina Falcón, Natalie Espinoza, Luis Solano R, Luis A Milla, Esther Hernandez-SanMiguel, Vicente A Torres, Pilar Sanchez-Gomez, Verónica Palma
Neogenin-1 (NEO1) is a transmembrane receptor involved in axonal guidance, angiogenesis, neuronal cell migration and cell death, during both embryonic development and adult homeostasis. It has been described as a dependence receptor, because it promotes cell death in the absence of its ligands (Netrin and Repulsive Guidance Molecule (RGM) families) and cell survival when they are present. Although NEO1 and its ligands are involved in tumor progression, their precise role in tumor cell survival and migration remain unclear...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28033683/snare-proteins-play-a-role-in-motor-axon-guidance-in-vertebrates-and-invertebrates
#15
Pablo José Barrecheguren, Oriol Ros, Tiziana Cotrufo, Beat Kunz, Eduardo Soriano, Fausto Ulloa, Esther T Stoeckli, Sofia J Araújo
Axonal growth and guidance rely on correct growth cone responses to guidance cues, both in the central nervous system (CNS) and in the periphery. Unlike the signaling cascades that link axonal growth to cytoskeletal dynamics, little is known about the crosstalk mechanisms between guidance and membrane dynamics and turnover in the axon. Our studies have shown that Netrin-1/Deleted in Colorectal Cancer (DCC) signaling triggers exocytosis through the SNARE Syntaxin-1 (STX-1) during the formation of commissural pathways...
December 29, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/28031116/-adipose-derived-stem-cell-transplantation-promotes-the-expression-of-netrin-1-in-the-rat-cortex-after-focal-cerebral-ischemia
#16
Jiehua Wang, Zhuquan Hong, Ying Pan, Guoqian Li
Objective To observe the effect of adipose-derived stem cells (ADSCs) transplantation on the expression of netrin-1 in rats after focal cerebral ischemia. Methods Male SD rats were randomly divided into control group, model group and ADSC group. ADSCs were harvested and purified. Focal cerebral ischemia models were established in rats by the suture method. ADSCs were injected into the lateral ventricle of ADSC group rats and the same does of PBS was given to model group rats. At day 4, 7 and 14 after reperfusion, six rats were sacrificed to remove the brain tissues at each time point...
January 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28004124/attenuation-of-neointimal-formation-with-netrin-1-and-netrin-1-preconditioned-endothelial-progenitor-cells
#17
Norika Mengchia Liu, Kin Lung Siu, Ji Youn Youn, Hua Cai
: Restenosis after angioplasty is a serious clinical problem that can result in re-occlusion of the coronary artery. Although current drug-eluting stents have proved to be more effective in reducing restenosis, they have drawbacks of inhibiting reendothelialization to promote thrombosis. New treatment options are in urgent need. We have shown that netrin-1, an axon-guiding protein, promotes angiogenesis and cardioprotection via production of nitric oxide (NO). The present study examined whether and how netrin-1 attenuates neointimal formation in a femoral wire injury model...
December 21, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27993028/nanocontact-printing-of-proteins-on-physiologically-soft-substrates-to-study-cell-haptotaxis
#18
Donald MacNearney, Bernard Mak, Grant Ongo, Timothy E Kennedy, David Juncker
Surface bound guidance cues and gradients are vital for directing cellular processes during development and repair. In vivo, these cues are often presented within a soft extracellular matrix with elastic moduli E < 10 kPa, but in vitro haptotaxis experiments have been conducted primarily on hard substrates with elastic moduli in the MPa to GPa range. Here, a technique is presented for patterning haptotactic proteins with nanometer resolution on soft substrates with physiological elasticity. A new nanocontact printing process was developed that circumvented the use of plasma activation that was found to alter the mechanical properties of the substrate...
December 20, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27939705/embryonic-axon-guidance-insights-from-drosophila-and-other-insects
#19
REVIEW
Timothy A Evans
During embryonic development, growing axons are guided by cellular signaling pathways that control a series of individual axon guidance decisions. In Drosophila, two major pathways (Netrin-Frazzled/DCC and Slit-Robo) regulate axon guidance in the embryonic ventral nerve cord, including the critical decision of whether or not to cross the midline. Studies in the fruit fly have revealed a complex picture of precise regulation and cross-talk between these pathways. In addition, Robo receptors in Drosophila have diversified their activities to regulate additional axon guidance decisions in the developing embryo...
December 2016: Current Opinion in Insect Science
https://www.readbyqxmd.com/read/27920664/investigation-of-snp-rs2060546-immediately-upstream-to-ntn4-in-a-danish-gilles-de-la-tourette-syndrome-cohort
#20
Shanmukha S Padmanabhuni, Rayan Houssari, Ann-Louise Esserlind, Jes Olesen, Thomas M Werge, Thomas F Hansen, Birgitte Bertelsen, Fotis Tsetsos, Peristera Paschou, Zeynep Tümer
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterized by multiple motor and vocal tics. GTS is a complex disorder, with environmental factors and several genes involved. Although variations within a few genes such as AADAC, NRXN1, SLITRK1, HDC, and IMMP2L have been tentatively associated with GTS (in a small number of patients), the causative genes underlying GTS pathophysiology remain unknown. In a previous genome-wide association study (GWAS) a single nucleotide polymorphism (SNP, rs2060546) near the Netrin-4 (NTN4 - MIM 610401) gene was shown to be associated with GTS [odds ratio (OR) = 1...
2016: Frontiers in Neuroscience
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