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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...
March 23, 2017: 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)
Ekrem Dere, Daniela Winkler, Caroline Ritter, Anja Ronnenberg, Giulia Poggi, Julia Patzig, Manuela Gernert, Christian Müller, Klaus-Armin Nave, Hannelore Ehrenreich, Hauke B Werner
The neuronal tetraspan proteins, M6A (Gpm6a) and M6B (Gpm6b), belong to the family of proteolipids that are widely expressed in the brain. We recently reported Gpm6a deficiency as a monogenetic cause of claustrophobia in mice. Its homolog proteolipid, Gpm6b, is ubiquitously expressed in neurons and oligodendrocytes. Gpm6b is involved in neuronal differentiation and myelination. It interacts with the N-terminal domain of the serotonin transporter (SERT) and decreases cell-surface expression of SERT. In the present study, we employed Gpm6b null mutant mice (Gpm6b(-/-)) to search for behavioral functions of Gpm6b...
January 15, 2015: Behavioural Brain Research
Stefanie L Butland, Shaun S Sanders, Mandi E Schmidt, Sean-Patrick Riechers, David T S Lin, Dale D O Martin, Kuljeet Vaid, Rona K Graham, Roshni R Singaraja, Erich E Wanker, Elizabeth Conibear, Michael R Hayden
HIP14 is the most highly conserved of 23 human palmitoyl acyltransferases (PATs) that catalyze the post-translational addition of palmitate to proteins, including huntingtin (HTT). HIP14 is dysfunctional in the presence of mutant HTT (mHTT), the causative gene for Huntington disease (HD), and we hypothesize that reduced palmitoylation of HTT and other HIP14 substrates contributes to the pathogenesis of the disease. Here we describe the yeast two-hybrid (Y2H) interactors of HIP14 in the first comprehensive study of interactors of a mammalian PAT...
August 1, 2014: Human Molecular Genetics
Melisa C Monteleone, Ezequiela Adrover, María Eugenia Pallarés, Marta C Antonelli, Alberto C Frasch, Marcela A Brocco
Prenatal stress (PS) exerts strong impact on fetal brain development and on adult offspring brain functions. Previous work demonstrated that chronic stress alters the mRNA expression of GPM6A, a neuronal glycoprotein involved in filopodium extension. In this work, we analyzed the effect of PS on gpm6a expression and the epigenetic mechanisms involved. Pregnant Wistar rats received restraint stress during the last week of gestation. Male offspring were sacrificed on postnatal days 28 and 60. Hippocampus and prefrontal cortex samples were analyzed for gene expression (qPCR for mRNAs and microRNAs), methylation status (bisulfite conversion) and protein levels...
January 2014: Epigenetics: Official Journal of the DNA Methylation Society
A El-Kordi, A Kästner, S Grube, M Klugmann, M Begemann, S Sperling, K Hammerschmidt, C Hammer, B Stepniak, J Patzig, P de Monasterio-Schrader, N Strenzke, G Flügge, H B Werner, R Pawlak, K-A Nave, H Ehrenreich
Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress...
2013: Translational Psychiatry
Mi-Hyun Park, Soo Heon Kwak, Kwang Joong Kim, Min Jin Go, Hye-Ja Lee, Kyung-Seon Kim, Joo-Yeon Hwang, Kuchan Kimm, Young-Min Cho, Hong Kyu Lee, Kyong Soo Park, Jong-Young Lee
The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candidate genes within linkage regions to identify genetic variants that predispose individuals to being overweight and developing type 2 diabetes...
2013: Experimental & Molecular Medicine
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