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https://www.readbyqxmd.com/read/29351997/spatiotemporal-organization-of-exocytosis-emerges-during-neuronal-shape-change
#1
Fabio L Urbina, Shawn M Gomez, Stephanie L Gupton
Neurite elongation and branching in developing neurons requires plasmalemma expansion, hypothesized to occur primarily via exocytosis. We posited that exocytosis in developing neurons and nonneuronal cells would exhibit distinct spatiotemporal organization. We exploited total internal reflection fluorescence microscopy to image vesicle-associated membrane protein (VAMP)-pHluorin-mediated exocytosis in mouse embryonic cortical neurons and interphase melanoma cells, and developed computer-vision software and statistical tools to uncover spatiotemporal aspects of exocytosis...
January 19, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29343638/commissural-neurons-transgress-the-cns-pns-boundary-in-absence-of-ventricular-zone-derived-netrin-1
#2
Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Heike Blockus, Chloé Dominici, Pavol Zelina, Patrick Mehlen, Alain Chédotal
During the development of the central nervous system (CNS), only motor axons project into peripheral nerves. Little is known about the cellular and molecular mechanisms that control the development of a boundary at the CNS surface and prevent CNS neuron emigration from the neural tube. It has previously been shown that a subset of spinal cord commissural axons abnormally invades sensory nerves in Ntn1 hypomorphic embryos and Dcc knockouts. However, whether netrin 1 also plays a similar role in the brain is unknown...
January 17, 2018: Development
https://www.readbyqxmd.com/read/29328435/mir%C3%A2-214-reduces-cisplatin-resistance-by-targeting-netrin%C3%A2-1-in-bladder-cancer-cells
#3
Jiao Liu, Jianbin Bi, Zeliang Li, Zhenhua Li, Xiankui Liu, Chuize Kong
miR‑214 has been reported to be downregulated in several cancer types, such as bladder cancer. However, its involvement in apoptosis and chemoresistance has not been investigated. The present study aimed to clarify the biological function of miR‑214 and potential mechanisms in chemoresistance of bladder cancer cells. Reverse transcription‑quantitative polymerase chain reaction demonstrated that miR‑214 was downregulated in bladder cancer tissues compared with the level in normal tissues. miR‑214 was downregulated in bladder cancer cell lines compared with the level in the normal cell line SV‑HUC‑1...
January 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29314827/macrophage-specific-in-vivo-gene-editing-using-cationic-lipid-assisted-polymeric-nanoparticles
#4
Ying-Li Luo, Cong-Fei Xu, Hong-Jun Li, Zhi-Ting Cao, Jing Liu, Ji-Long Wang, Xiao-Jiao Du, Xian-Zhu Yang, Zhen Gu, Jun Wang
The CRISPR/Cas9 gene editing technology holds promise for the treatment of multiple diseases. However, the inability to perform specific gene editing in targeted tissues and cells, which may cause off-target effects, is one of the critical bottlenecks for therapeutic application of CRISPR/Cas9. Herein, macrophage-specific promoter-driven Cas9 expression plasmids (pM458 and pM330) were constructed and encapsulated in cationic lipid-assisted PEG-b-PLGA nanoparticles (CLAN). The obtained nanoparticles encapsulating the CRISPR/Cas9 plasmids were able to specifically express Cas9 in macrophages as well as their precursor monocytes both in vitro and in vivo...
January 9, 2018: ACS Nano
https://www.readbyqxmd.com/read/29307055/novel-acute-kidney-injury-biomarkers-their-characteristics-utility-and-concerns
#5
REVIEW
Braian M Beker, Mateo G Corleto, Cecilia Fieiras, Carlos G Musso
Acute kidney injury (AKI) consists of a rapid renal function decline which usually increases serum urea and creatinine levels. Since kidney injury begins by inducing biological and molecular changes which evolve to cellular damage, biomarkers could be used as tools for monitoring early AKI appearance, and predicting its recovery. Among the main AKI biomarkers the neutrophil gelatinase-associated lipocalin, cystatin C, kidney injury molecule-1, monocyte chemotactic peptide-1, N-acetyl-β-D-glucosaminidase, interleukin-18, liver-type fatty acid-binding protein, netrin-1, cycle arrest markers, endogenous ouabain, selenium-binding protein 1, and BPIFA2 marker, have been described...
January 6, 2018: International Urology and Nephrology
https://www.readbyqxmd.com/read/29305865/netrin-1-promotes-metastasis-of-gastric-cancer-by-regulating-yap-activity
#6
Kai Yin, Shengchun Dang, Lei Cui, Xin Fan, Rong Xie, Jianguo Qu, Mengyuan Shang, Jixiang Chen
Yes-associated protein (YAP) is a major downstream molecular of the Hippo pathway, which plays important role in cancer development. Netrin-1 conveys oncogenic activity in many types of malignant tumors. However, the downstream signaling of netrin-1 mediating its oncogenic effects in gastric cancer (GC) is not well defined. Here, we aim to investigate the role of netrin-1 in metastasis potential of GC by regulating YAP. In this study, we showed that netrin-1 inhibition significantly decreased migration and invasion abilities of GC cells, while netrin-1 overexpression effectively reversed this effect...
January 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29277614/hepatocellular-carcinoma-associated-depletion-of-the-netrin-1-receptor-uncoordinated-phenotype-5a-unc5a-skews-the-hepatic-unfolded-protein-response-towards-prosurvival-outcomes
#7
Romain Barnault, Thomas Lahlali, Marie-Laure Plissonnier, Cristina Romero-López, Noémie Laverdure, Benjamin Ducarouge, Michel Rivoire, Patrick Mehlen, Fabien Zoulim, Romain Parent
In the liver, HBV and HCV infections, exposure to toxics, genetic and metabolic disorders may induce endoplasmic reticulum (ER) stress and the unfolding protein response (UPR). The UPR allows cells to reach ER homeostasis after lumen overload, but also fosters survival of damaged cells and therefore HCC onset. Dependence receptors such as UNC5A trigger apoptosis when unbound to their ligands. We have previously shown that the main dependence receptor ligand, netrin-1, could protect cells against UPR-induced apoptosis through sustained translation...
December 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29276694/an-optimized-immunohistochemistry-protocol-for-detecting-the-guidance-cue-netrin-1-in-neural-tissue
#8
Samer Salameh, Dominique Nouel, Cecilia Flores, Daniel Hoops
Netrin-1, an axon guidance protein, is difficult to detect using immunohistochemistry. We performed a multi-step, blinded, and controlled protocol optimization procedure to establish an efficient and effective fluorescent immunohistochemistry protocol for characterizing Netrin-1 expression. Coronal mouse brain sections were used to test numerous antigen retrieval methods and combinations thereof in order to optimize the stain quality of a commercially available Netrin-1 antibody. Stain quality was evaluated by experienced neuroanatomists for two criteria: signal intensity and signal-to-noise ratio...
2018: MethodsX
https://www.readbyqxmd.com/read/29234153/netrin-1-elicits-metastatic-potential-of-non-small-cell-lung-carcinoma-cell-by-enhancing-cell-invasion-migration-and-vasculogenic-mimicry-via-emt-induction
#9
Xiaofei Zhang, Ping Cui, Beichen Ding, Yuening Guo, Kaiyu Han, Jianing Li, Hong Chen, Wei Zhang
Ectopic expression of netrin-1 has been validated in several cancers including non-small cell lung cancer (NSCLC). Recent research confirms the critical role of netrin-1 in NSCLC growth and its prognostic value. Unfortunately, its contribution in NSCLC metastasis remains elusive. Here, netrin-1 had relatively high expression in NSCLC tissues and cells, especially in high metastatic groups. Notably, netrin-1 overexpression aggravated the malignant metastatic behavior of NSCLC cells, including cell invasion, migration, and vasculogenic mimicry (VM), whereas netrin-1 depression reversely dampened the metastatic potential...
December 12, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/29209172/the-role-of-netrin-1-in-improving-functional-recovery-through-autophagy-stimulation-following-spinal-cord-injury-in-rats
#10
Liangjie Bai, Xifan Mei, Yanfeng Wang, Yajiang Yuan, Yunlong Bi, Gang Li, Hongyu Wang, Peng Yan, Gang Lv
Our previous findings indicated that treatment with Netrin-1 could improve functional recovery through the stimulation of autophagy, by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway in rats following spinal cord injury (SCI). However, the underlying mechanisms were not elucidated. The purpose of this study was to investigate the underlying mechanisms by which Netrin-1 promotes autophagy and improves functional recovery after SCI. Following controlled SCI in Sprague-Dawley rats, we observed that the autophagic flux in neurons was impaired, as reflected by the accumulation of light chain 3-II (LC3-II)-positive and LC3-positive autophagosomes (APs), accompanied by the accumulation of the autophagic substrate, Sequestosome 1 (SQSTM1; also known as p62)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29202173/dcc-ntn1-complex-mutations-in-patients-with-congenital-hypogonadotropic-hypogonadism-impair-gnrh-neuron-development
#11
Justine Bouilly, Andrea Messina, Georgios Papadakis, Daniele Cassatella, Cheng Xu, James S Acierno, Brooke Tata, Gerasimos Sykiotis, Sara Santini, Yisrael Sidis, Eglantine Elowe-Gruau, Franziska Phan-Hug, Michael Hauschild, Pierre-Marc Bouloux, Richard Quinton, Mariarosaria Lang-Muritano, Lucie Favre, Laura Marino, Paolo Giacobini, Andrew A Dwyer, Nicolas J Niederländer, Nelly Pitteloud
Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease characterized by absent puberty and infertility due to GnRH deficiency, and is often associated with anosmia (Kallmann syndrome, KS). The genetic etiology of CHH is heterogeneous, and more than 30 genes have been implicated in approximately 50% of patients with CHH. We hypothesized that genes encoding axon-guidance proteins containing fibronectin type-III (FN3) domains (similar to ANOS1, the first gene associated with KS), are mutated in CHH...
November 30, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29199452/semaphorin-3a-and-netrin-1-predict-the-development-of-kidney-injury-in-children-with-congenital-hydronephrosis
#12
Xiaobing Li, Xianghua Liu, Ji Li, ELi Song, Ning Sun, Wen Liu, Tian Wang, Jinchang Yang, Zhenzhen Li
Congenital obstructive nephropathy is amongst the main causes of chronic renal failure in children. Early diagnosis and initiation of the treatment will delay progressive renal tubular atrophy and interstitial fibrosis with the loss of nephrons. The aim of this study was to evaluate whether urinary (u) semaphorin-3A (SEMA-3A) and Netrin-1 may be potential biomarkers in children with congenital hydronephrosis due to ureteropelvic junction obstruction (UPJO). The study consisted of 42 children with severe hydronephrosis who needed surgery and two control groups (Control One: 42 children with mild, non-obstructive hydronephrosis; Control Two: 44 healthy children)...
December 3, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29187730/genome-wide-analysis-in-uk-biobank-identifies-four-loci-associated-with-mood-instability-and-genetic-correlation-with-major-depressive-disorder-anxiety-disorder-and-schizophrenia
#13
Joey Ward, Rona J Strawbridge, Mark E S Bailey, Nicholas Graham, Amy Ferguson, Donald M Lyall, Breda Cullen, Laura M Pidgeon, Jonathan Cavanagh, Daniel F Mackay, Jill P Pell, Michael O'Donovan, Valentina Escott-Price, Daniel J Smith
Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD)...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29185158/delivery-of-expression-constructs-of-secreted-frizzled-related-protein-4-and-its-domains-by-chitosan-dextran-sulfate-nanoparticles-enhances-their-expression-and-anti-cancer-effects
#14
Vanathi Perumal, Frank Arfuso, Yan Chen, Simon Fox, Arun M Dharmarajan
In malignant mesothelioma (MM) cells, secreted frizzled-related protein 4 (SFRP4) expression is downregulated by promoter methylation. In this study, we evaluated the effect of encapsulated chitosan-dextran (CS-DS) nanoparticle formulations of SFRP4 and its cysteine-rich domain (CRD) and netrin-like domain (NLD) as means of SFRP4-GFP protein delivery and their effects in JU77 and ONE58 MM cell lines. CS-DS formulations of SFRP4, CRD, and NLD nanoparticles were prepared by a complex coacervation technique, and particle size ranged from 300 nm for empty particles to 337 nm for particles containing the proteins...
November 28, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29162556/recombinant-netrin-1-binding-unc5b-receptor-attenuates-neuroinflammation-and-brain-injury-via-ppar%C3%AE-nf%C3%AE%C2%BAb-signaling-pathway-after-subarachnoid-hemorrhage-in-rats
#15
Zongyi Xie, Lei Huang, Budbazar Enkhjargal, Cesar Reis, Weifeng Wan, Jiping Tang, Yuan Cheng, John H Zhang
Neuroinflammation is an essential mechanism involved in the pathogenesis of subarachnoid hemorrhage (SAH)-induced brain injury. Recently, Netrin-1 (NTN-1) is well established to exert anti-inflammatory property in non-nervous system diseases through inhibiting infiltration of neutrophil. The present study was designed to investigate the effects of NTN-1 on neuroinflammation, and the potential mechanism in a rat model of SAH. Two hundred and ninety-four male Sprague Dawley rats (weight 280-330 g) were subjected to the endovascular perforation model of SAH...
November 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29161591/cell-invasion-in%C3%A2-vivo-via-rapid-exocytosis-of-a-transient-lysosome-derived-membrane-domain
#16
Kaleb M Naegeli, Eric Hastie, Aastha Garde, Zheng Wang, Daniel P Keeley, Kacy L Gordon, Ariel M Pani, Laura C Kelley, Meghan A Morrissey, Qiuyi Chi, Bob Goldstein, David R Sherwood
Invasive cells use small invadopodia to breach basement membrane (BM), a dense matrix that encases tissues. Following the breach, a large protrusion forms to clear a path for tissue entry by poorly understood mechanisms. Using RNAi screening for defects in Caenorhabditis elegans anchor cell (AC) invasion, we found that UNC-6(netrin)/UNC-40(DCC) signaling at the BM breach site directs exocytosis of lysosomes using the exocyst and SNARE SNAP-29 to form a large protrusion that invades vulval tissue. Live-cell imaging revealed that the protrusion is enriched in the matrix metalloprotease ZMP-1 and transiently expands AC volume by more than 20%, displacing surrounding BM and vulval epithelium...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29158083/unc-5-netrin-receptor-b-mediates-osteogenic-differentiation-by-modulating-bone-morphogenetic-protein-signaling-in-human-adipose-derived-stem-cells
#17
Xinyi Hu, Yunsong Liu, Min Zhang, Yuejun Wang, Longwei Lv, Xiao Zhang, Ping Zhang, Yongsheng Zhou
UNC-5 netrin receptor B (UNC5B) is a dependence receptor of netrin-1 that plays an essential role in mediating angiogenesis and tumorigenesis. Despite its significant roles, there is limited knowledge about the role played by UNC5B in osteogenesis. In the present study, we first demonstrated that UNC5B was required for osteogenic differentiation of human adipose-derived stem cells (hASCs), both in vitro and in vivo. We also found that mechanistically, UNC5B promotes osteogenic differentiation by activating bone morphogenetic protein signaling...
November 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29156815/the-effect-of-aspirin-on-circulating-netrin-1-levels-in-humans-is-dependent-on-the-inflammatory-status-of-the-vascular-endothelium
#18
Kerry Layne, Timothy Goodman, Albert Ferro, Gabriella Passacquale
In atherosclerotic animal models, the cyclo-oxygenase (COX)-inhibitor aspirin counteracts downregulation of endothelial-derived netrin-1, thus reducing arterial inflammation. We here explored the effect of aspirin on netrin-1 in healthy subjects undergoing influenza immunisation, which is an established experimental model of inflammation-related endothelial dysfunction. Our data showed that netrin-1 undergoes reduction (-29.25% from baseline; p=0.0017) in the presence of endothelial activation (VCAM-1 rose by 9...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154364/non-contingent-exposure-to-amphetamine-in-adolescence-recruits-mir-218-to-regulate-dcc-expression-in-the-vta
#19
Santiago Cuesta, José Maria Restrepo-Lozano, Steven Silvestrin, Dominique Nouel, Angélica Torres-Berrio, Lauren M Reynolds, Andreas Arvanitogiannis, Cecilia Flores
The development of the dopamine input to the medial prefrontal cortex occurs during adolescence and is a process that is vulnerable to disruption by stimulant drugs such as amphetamine. We have previously linked the amphetamine-induced disruption of dopamine connectivity and prefrontal cortex maturation during adolescence to the downregulation of the Netrin-1 receptor, DCC, in dopamine neurons. However, how DCC expression in dopamine neurons is itself regulated is completely unknown. MicroRNA (miRNA) regulation of mRNA translation and stability is a prominent mechanism linking environmental events to changes in protein expression...
November 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29141180/motor-neuron-migration-and-positioning-mechanisms-new-roles-for-guidance-cues
#20
REVIEW
Minkyung Kim, Brielle Bjorke, Grant S Mastick
Motor neurons differentiate from progenitor cells and cluster as motor nuclei, settling next to the floor plate in the brain stem and spinal cord. Although precise positioning of motor neurons is critical for their functional input and output, the molecular mechanisms that guide motor neurons to their proper positions remain poorly understood. Here, we review recent evidence of motor neuron positioning mechanisms, highlighting situations in which motor neuron cell bodies can migrate, and experiments that show that their migration is regulated by axon guidance cues...
November 12, 2017: Seminars in Cell & Developmental Biology
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