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Changguo Ma, Chunjie Gu, Yongxia Huo, Xiaoyan Li, Xiong-Jian Luo
Genome-wide association studies (GWAS) have identified more than 100 loci that show robust association with schizophrenia risk. However, due to the complexity of linkage disequilibrium and gene regulatory, it is challenging to pinpoint the causal genes at the risk loci and translate the genetic findings from GWAS into disease mechanism and clinical treatment. Here we systematically predicted the plausible candidate causal genes for schizophrenia at genome-wide level. We utilized different approaches and strategies to predict causal genes for schizophrenia, including Sherlock, SMR, DAPPLE, Prix Fixe, NetWAS, and DEPICT...
March 15, 2018: Translational Psychiatry
Camilla Maria Falch, Arvind Y M Sundaram, Kristin Astrid Øystese, Kjersti Ringvoll Normann, Tove Lekva, Ivars Silamikelis, Alexander Kirkeby Eieland, Marianne Andersen, Jens Bollerslev, Nicoleta Cristina Olarescu
OBJECTIVE: Reliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast- and slow-growing GAs present different gene expression profiles and reliable biomarkers for tumor growth potential could be identified, focusing on the specific role of epithelial-mesenchymal transition (EMT). DESIGN AND METHODS: Eight GAs selected for RNA sequencing were equally divided into fast- and slow-growing group by the tumor volume doubling time (TVDT) median (27...
March 2018: European Journal of Endocrinology
Yasuyuki Ito, Atsuko Honda, Michihiro Igarashi
Neuronal development is composed of the complex steps which involve many signaling proteins. On the other hand, there are many proteins highly expressed in the differentiated neurons at developmental stages, but of which physiological functions are not precisely known so far. Glycoprotein 6a (GPM6a) currently belongs to such proteins. This protein has four-transmembrane domains and is a member of proteolipid protein family. Recently, we demonstrated that GPM6a is highly concentrated in lipid rafts of the developing neuron with its palmitoylation, and that this molecule is involved in rapid determination of the neuronal polarity, in response to laminin, an extracellular matrix protein (Honda et al...
March 2018: Neuroscience Research
Atsuko Honda, Hiroshi Usui, Kenji Sakimura, Michihiro Igarashi
RUN and FYVE domain-containing 3 (Rufy3) is an adapter protein for small GTPase proteins and is bound to activated Rap2, a Ras family protein in the developing neuron. Previously, we reported the presence of a rapid cell polarity determination mechanism involving Rufy3, which is likely required for in vivo neuronal development. However, the molecular details of this mechanism are unclear. To this end, here we produced Rufy3 knock-out (Rufy3-KO) mice to study the role of Rufy3 in more detail. Examining Rufy3-KO neurons, we found that Rufy3 is recruited via glycoprotein M6A to detergent-resistant membrane domains, which are biochemically similar to lipid rafts...
December 22, 2017: Journal of Biological Chemistry
Michel Fausther, Elise G Lavoie, Jonathan A Dranoff
Liver myofibroblasts are specialized effector cells that drive hepatic fibrosis, a hallmark process of chronic liver diseases, leading to progressive scar formation and organ failure. Liver myofibroblasts are increasingly recognized as heterogeneous with regards to their origin, phenotype, and functions. For instance, liver myofibroblasts express cell markers that are universally represented such as, ItgαV and Pdgfrβ, or restricted to a given subpopulation such as, Lrat exclusively expressed in hepatic stellate cells, and Gpm6a in mesothelial cells...
2017: PloS One
Xi Gu, Congcong Fu, Lifang Lin, Shuhu Liu, Xiaohong Su, Aili Li, Qiaoqi Wu, Chunhong Jia, Peidong Zhang, Lu Chen, Xinhong Zhu, Xuemin Wang
The class IIa histone deacetylases (HDACs) play important roles in the central nervous system during diverse biological processes such as synaptic plasticity, axon regeneration, cell apoptosis, and neural differentiation. Although it is known that HDAC5 regulates neuronal differentiation, neither the physiological function nor the regulation of HDAC5 in neuronal differentiation is clear. Here, we identify HDAC5 as an inhibitor of neurite elongation and show that HDAC5 is regulated by the brain enriched microRNA miR-124 and miR-9...
January 2018: Journal of Cellular Physiology
Atsuko Honda, Yasuyuki Ito, Kazuko Takahashi-Niki, Natsuki Matsushita, Motohiro Nozumi, Hidenori Tabata, Kosei Takeuchi, Michihiro Igarashi
Lipid raft domains, where sphingolipids and cholesterol are enriched, concentrate signaling molecules. To examine how signaling protein complexes are clustered in rafts, we focused on the functions of glycoprotein M6a (GPM6a), which is expressed at a high concentration in developing mouse neurons. Using imaging of lipid rafts, we found that GPM6a congregated in rafts in a GPM6a palmitoylation-dependent manner, thereby contributing to lipid raft clustering. In addition, we found that signaling proteins downstream of GPM6a, such as Rufy3, Rap2, and Tiam2/STEF, accumulated in lipid rafts in a GPM6a-dependent manner and were essential for laminin-dependent polarity during neurite formation in neuronal development...
April 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Hong-Bo Shi, Jin-Li Lou, Hong-Lin Shi, Feng Ren, Yu Chen, Zhong-Ping Duan
AIM: To prepare a Gpm6a/Reelin(GFPCreERT2) construct with a rapid and reliable strategy using a bacterial artificial chromosome (BAC). METHODS: Gpm6a and Reelin BACs were purified and transformed into SW102 E. coli by electroporation. The GFPCreERT2 fragment was prepared from a shuttle vector and transformed into SW102 E. coli carrying a BAC. Homologous recombination was induced in SW102 E. coli. Recombinant clones were screened and confirmed by PCR and restriction enzyme digestion...
January 14, 2017: World Journal of Gastroenterology: WJG
Karina Formoso, Micaela D Garcia, Alberto C Frasch, Camila Scorticati
Neuronal glycoprotein M6a belongs to the tetraspan proteolipid protein (PLP) family. Mutations in GPM6A gene have been related to mental disorders like schizophrenia, bipolar disorders and claustrophobia. M6a is expressed mainly in neuronal cells of the central nervous system and it has been extensively related to neuronal plasticity. M6a induces neuritogenesis and axon/filopodium outgrowth; however its mechanism of action is still unresolved. We recently reported that the integrity of the transmembrane domains (TMDs) 2 and 4 are critical for M6a filopodia induction...
December 2016: Molecular and Cellular Neurosciences
Anabel Alvarez Juliá, Alberto C Frasch, Beata Fuchsova
Stress-responsive neuronal membrane glycoprotein M6a (Gpm6a) functions in neurite extension, filopodium and spine formation and synaptogenesis. The mechanisms of Gpm6a action in these processes are incompletely understood. Previously, we identified the actin regulator coronin-1a (Coro1a) as a putative Gpm6a interacting partner. Here, we used co-immunoprecipitation assays with the anti-Coro1a antibody to show that Coro1a associates with Gpm6a in rat hippocampal neurons. By immunofluorescence microscopy, we demonstrated that in hippocampal neurons Coro1a localizes in F-actin-enriched regions and some of Coro1a spots co-localize with Gpm6a labeling...
April 2016: Journal of Neurochemistry
Ingrid Lua, Yuchang Li, Jessica A Zagory, Kasper S Wang, Samuel W French, Jean Sévigny, Kinji Asahina
BACKGROUND & AIMS: Contribution of hepatic stellate cells (HSCs), portal fibroblasts (PFs), and mesothelial cells (MCs) to myofibroblasts is not fully understood due to insufficient availability of markers and isolation methods. The present study aimed to isolate these cells, characterize their phenotypes, and examine their contribution to myofibroblasts in liver fibrosis. METHODS: Liver fibrosis was induced in Collagen1a1-green fluorescent protein (Col1a1(GFP)) mice by bile duct ligation (BDL), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet, or CCl4 injections...
May 2016: Journal of Hepatology
Liangdong Chen, Deqiang Zhuo, Jiakuan Chen, Hongyin Yuan
Lung carcinoma is the most common and aggressive malignant tumor with poor clinical outcome. Identification of new marker of lung cancer is essential for the diagnosis and prognosis of the disease. To identify differentially expressed genes (DEGs) and find associated pathways that may function as targets of lung cancer. Gene expression profiling of GSE40791 were downloaded from GEO (Gene Expression Omnibus), including 100 normal specimens and 94 lung cancer samples. The DEGs were screened out by LIMMA package in R language...
2015: International Journal of Clinical and Experimental Medicine
Mi Young Ahn, Min-Ji Kim, Ryun Hee Kwon, Jae Sam Hwang, Kun-Koo Park
BACKGROUND: Molecular genetic mechanisms underlying the anti-inflammatory effects of ethanol extract (GB) from G. bimaculatus, a type of cricket, are not fully elucidated. G. bimaculatus was reported to be rich in unsaturated fatty acid and to decrease the omega-6/omega-3 fatty acid ratio when fed to chickens. GB may reduce the amount of fat or increase the unsaturated fatty acid ratio. METHODS: Male Wistar rats fed a high-fat diet (HFD) were orally administered with 5 groups: phosphate buffered saline (PBS, control), GB (100 mg/kg or 200 mg/kg), Pravastatin or Isaria sinclairii (IS) extract, which is reported to have fat-reducing effects, for either 1 or 2 months...
2015: Lipids in Health and Disease
Brian A McCarthy, Sophia Yancopoulos, Mike Tipping, Xiao-Jie Yan, Xue Ping Wang, Fiona Bennett, Wentian Li, Martin Lesser, Santanu Paul, Erin Boyle, Carolina Moreno, Rosa Catera, Bradley T Messmer, Giovanna Cutrona, Manlio Ferrarini, Jonathan E Kolitz, Steven L Allen, Kanti R Rai, Andrew C Rawstron, Nicholas Chiorazzi
Chronic lymphocytic leukemia (CLL) is a clonal disease of B lymphocytes manifesting as an absolute lymphocytosis in the blood. However, not all lymphocytoses are leukemic. In addition, first-degree relatives of CLL patients have an ~15 % chance of developing a precursor condition to CLL termed monoclonal B cell lymphocytosis (MBL), and distinguishing CLL and MBL B lymphocytes from normal B cell expansions can be a challenge. Therefore, we selected FMOD, CKAP4, PIK3C2B, LEF1, PFTK1, BCL-2, and GPM6a from a set of genes significantly differentially expressed in microarray analyses that compared CLL cells with normal B lymphocytes and used these to determine whether we could discriminate CLL and MBL cells from B cells of healthy controls...
December 2015: Immunologic Research
Esmaeil Ebrahimie, Zahra Nurollah, Mansour Ebrahimi, Farhid Hemmatzadeh, Jagoda Ignjatovic
Pandemic influenza remains as a substantial threat to humans with a widespread panic worldwide. In contrast, seasonal (non-pandemic) has a mild non-lethal infection each year. The underlying mechanisms governing the detrimental effects of pandemic influenza are yet to be known. Transcriptomic-based network discovery and gene ontology (GO) analysis of host response to pandemic influenza, compared to seasonal influenza, can shed light on the differential mechanisms which pandemic influenza is employed during evolution...
September 2015: Molecular Biology Reports
Karina Formoso, Micaela D García, Alberto C Frasch, Camila Scorticati
Membrane glycoprotein M6a, which belongs to the tetraspan proteolipid protein family, promotes structural plasticity in neurons and cell lines by unknown mechanisms. This glycoprotein is encoded by Gpm6a, a stress-regulated gene. The hippocampus of animals chronically stressed by either psychosocial or physical stressors shows decreased M6a expression. Stressed Gpm6a-null mice develop a claustrophobia-like phenotype. In humans, de novo duplication of GPM6A results in learning/behavioral abnormalities, and two single-nucleotide polymorphisms (SNPs) in the non-coding region are linked to mood disorders...
August 2015: Journal of Neurochemistry
B Fuchsova, A Alvarez Juliá, H S Rizavi, A C Frasch, G N Pandey
BACKGROUND: Expression of the neuronal membrane glycoprotein M6a (GPM6A), the proteolipid protein (PLP/DM20) family member, is downregulated in the hippocampus of chronically stressed animals. Its neuroplastic function involves a role in neurite formation, filopodium outgrowth and synaptogenesis through an unknown mechanism. Disruptions in neuroplasticity mechanisms have been shown to play a significant part in the etiology of depression. Thus, the current investigation examined whether GPM6A expression is also altered in human depressed brain...
July 23, 2015: Neuroscience
Karina Formoso, Silvia C Billi, Alberto C Frasch, Camila Scorticati
Neuronal glycoprotein M6a is involved in neuronal plasticity, promoting neurite and filopodia outgrowth and, likely, synaptogenesis. Polymorphisms in the human M6a gene GPM6A have recently been associated with mental illnesses such as schizophrenia, bipolar disorders, and claustrophobia. Nevertheless, the molecular bases underlying these observations remain unknown. We have previously documented that, to induce filopodia formation, M6a depends on the association of membrane lipid microdomains and the activation of Src and mitogen-activated protein kinase kinases...
February 2015: Journal of Neuroscience Research
Anne Gregor, Jamie M Kramer, Monique van der Voet, Ina Schanze, Steffen Uebe, Rogier Donders, André Reis, Annette Schenck, Christiane Zweier
Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient-derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism...
December 2014: Human Mutation
Cyndia Charfi, Elsy Edouard, Eric Rassart
BACKGROUND: Previously, we found that the Graffi murine leukemia virus (MuLV) is able to induce a wide spectrum of hematologic malignancies in vivo. Using high-density oligonucleotide microarrays, we established the gene expression profiles of several of these malignancies, thereby specifically focusing on genes deregulated in the lymphoid sub-types. We observed over-expression of a variety of genes, including Arntl2, Bfsp2, Gfra2, Gpm6a, Gpm6b, Nln, Fbln1, Bmp7, Etv5 and Celsr1 and, in addition, provided evidence that Fmn2 and Parm-1 may act as novel oncogenes...
June 2014: Cellular Oncology (Dordrecht)
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