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Jun Ren, Tian Zhao, Yiliang Xu, Haihong Ye
Disrupted-in-schizophrenia 1 (DISC1), a gene susceptible for major mental illnesses, including schizophrenia, plays multiple roles in neural development, including neuronal proliferation, maturation, migration and neurite outgrowth. DISC1 regulates neurite length via interaction with several intracellular proteins, such as NDEL1, FEZ1 and dysbindin. However, the signal transduction mechanism upstream of DISC1 in regulating neurite outgrowth remains to be elucidated. Here we show that DISC1 interacts with the intracellular domain of close homolog of L1 (CHL1), a member of the L1 family of neural cell adhesion molecules...
October 1, 2016: Brain Research
Eugenia Butkevich, Wolfgang Härtig, Miroslav Nikolov, Christian Erck, Jens Grosche, Henning Urlaub, Christoph F Schmidt, Dieter R Klopfenstein, John Jia En Chua
Adapters bind motor proteins to cargoes and therefore play essential roles in Kinesin-1 mediated intracellular transport. The regulatory mechanisms governing adapter functions and the spectrum of cargoes recognized by individual adapters remain poorly defined. Here, we show that cargoes transported by the Kinesin-1 adapter FEZ1 are enriched for presynaptic components and identify that specific phosphorylation of FEZ1 at its serine 58 regulatory site is mediated by microtubule affinity-regulating kinases (MARK/PAR-1)...
2016: Scientific Reports
Mandy Johnstone, Alan Maclean, Lien Heyrman, An-Sofie Lenaerts, Annelie Nordin, Lars-Göran Nilsson, Peter De Rijk, Dirk Goossens, Rolf Adolfsson, David M St Clair, Jeremy Hall, Stephen M Lawrie, Andrew M McIntosh, Jurgen Del-Favero, Douglas H R Blackwood, Benjamin S Pickard
Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification...
October 2015: Molecular Neuropsychiatry
T I Vachev, V K Stoyanova, H Y Ivanov, I N Minkov, N T Popov
Schizophrenia (SZ) is a chronic neuropsychiatric disorder characterized by affective, neuromorphological and cognitive impairment, deteriorated social functioning and psychosis with underlying molecular abnormalities, including gene expression changes. Observations have suggested that fasciculation and elongation protein ζ-1 (FEZ1) may be implicated in the pathogenesis of schizophrenia. Nevertheless, our current knowledge of the expression of FEZ1 in peripheral blood of schizophrenia patients remains unclear...
June 2015: Balkan Journal of Medical Genetics: BJMG
A Sami Saribas, Pascale Coric, Anahit Hamazaspyan, William Davis, Rachael Axman, Martyn K White, Magid Abou-Gharbia, Wayne Childers, Jon H Condra, Serge Bouaziz, Mahmut Safak
Agnoprotein is an important regulatory protein of polyomaviruses, including JCV, BKV, and SV40. In the absence of its expression, these viruses are unable to sustain their productive life cycle. It is a highly basic phosphoprotein that localizes mostly to the perinuclear area of infected cells, although a small amount of the protein is also found in nucleus. Much has been learned about the structure and function of this important regulatory protein in recent years. It forms highly stable dimers/oligomers in vitro and in vivo through its Leu/Ile/Phe-rich domain...
October 2016: Journal of Cellular Physiology
Rajesh Mandarapu, Balakrishna Murthy Prakhya
The complex immune system displays a coordinated transcriptional response to xenobiotic exposure by altering expression of designated transcription factors that, in turn, trigger immune responses. Despite the identification of several transcription factors that contribute to regulatory response, very little is known about the specific role of factors that are triggered due to exposure to obnoxious pesticides. Here, for the first time, alterations in human peripheral blood lymphocyte expression of transcriptional factors - thrombospondin-1 (THBS-1), secretory phospho-protein-1 (SPP-1), glycoprotein non-metastatic-β (GPNMB) and fasciculation and elongation factor ζ-1 (FEZ-1), due to in vitro exposure to the crop protection chemicals cypermethrin and mancozeb are reported...
July 2016: Journal of Immunotoxicology
Taira Mayanagi, Hiroki Yasuda, Kenji Sobue
UNLABELLED: Dysregulation of synapse formation and plasticity is closely related to the pathophysiology of psychiatric and neurodevelopmental disorders. The prefrontal cortex (PFC) is particularly important for executive functions such as working memory, cognition, and emotional control, which are impaired in the disorders. PSD-Zip70 (Lzts1/FEZ1) is a postsynaptic density (PSD) protein predominantly expressed in the frontal cortex, olfactory bulb, striatum, and hippocampus. Here we found that PSD-Zip70 knock-out (PSD-Zip70KO) mice exhibit working memory and cognitive defects, and enhanced anxiety-like behaviors...
October 21, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Viacheslav Malikov, Eveline Santos da Silva, Vladimir Jovasevic, Geoffrey Bennett, Daniel A de Souza Aranha Vieira, Bianca Schulte, Felipe Diaz-Griffero, Derek Walsh, Mojgan H Naghavi
Intracellular transport of cargos, including many viruses, involves directed movement on microtubules mediated by motor proteins. Although a number of viruses bind motors of opposing directionality, how they associate with and control these motors to accomplish directed movement remains poorly understood. Here we show that human immunodeficiency virus type 1 (HIV-1) associates with the kinesin-1 adaptor protein, Fasiculation and Elongation Factor zeta 1 (FEZ1). RNAi-mediated FEZ1 depletion blocks early infection, with virus particles exhibiting bi-directional motility but no net movement to the nucleus...
March 30, 2015: Nature Communications
D O Omel'chenko, A A Rzhaninova, D V Gol'dshteĭn
Potential markers and the mechanism of the spontaneous transformation of multipotent stromal cells (MSC) with perivascular immunophenotype have been determined. A transcriptome comparative study was performed involving six paired specimens of normal and spontaneously transformed MSC with perivascular immunophenotype, obtained in the first passages following the isolation of adipose tissue of six healthy donors. According to the results obtained using the microarray Illumina HT-12 v4 with the Significance Analysis of Microarrays software, differentially expressed transcripts were revealed and a statistical analysis using Gene Ontology and Molecular Signatures Databases was conducted...
January 2014: Genetika
Wei Zhou, Mei-Rong He, Hong-Li Jiao, Liu-Qing He, Dan-Ling Deng, Juan-Juan Cai, Zhi-Yuan Xiao, Ya-Ping Ye, Yan-Qing Ding, Wen-Ting Liao, Si-De Liu
The Leucine zipper tumor suppressor gene 1 (LZTS1/FEZ1) gene was originally identified as a potential tumor suppressor. However, the expression pattern and the role of LZTS1 in the progression of colorectal cancer (CRC) have not been well characterized. Herein, we reported that LZTS1 was markedly reduced in CRC tissues compared with matched adjacent normal intestine epithelial tissues. In analysis of 160 CRC specimens, we revealed that decreased expression of LZTS1 was correlated to aggressive characteristics and poor survival of patients with CRC...
April 28, 2015: Cancer Letters
Masaya Tohyama, Shingo Miyata, Tsuyoshi Hattori, Shoko Shimizu, Shinsuke Matsuzaki
Recently several potential susceptibility genes for major psychiatric disorders (schizophrenia and major depression) such as disrupted-in-schizophrenia 1(DISC1), dysbindin and pituitary adenylate cyclase-activating polypeptide (PACAP) have been reported. DISC1 is involved in neural development directly via adhesion molecules or via its binding partners of DISC1 such as elongation protein ζ-1 (FEZ1), DISC1-binding zinc-finger protein (DBZ) and kendrin. PACAP also regulates neural development via stathmin 1 or via regulation of the DISC1-DBZ binding...
June 2015: Anatomical Science International
Natalie Spang, Anne Feldmann, Heike Huesmann, Fazilet Bekbulat, Verena Schmitt, Christof Hiebel, Ingrid Koziollek-Drechsler, Albrecht M Clement, Bernd Moosmann, Jennifer Jung, Christian Behrends, Ivan Dikic, Andreas Kern, Christian Behl
Macroautophagy is a degradative pathway that sequesters and transports cytosolic cargo in autophagosomes to lysosomes, and its deterioration affects intracellular proteostasis. Membrane dynamics accompanying autophagy are mostly elusive and depend on trafficking processes. RAB GTPase activating proteins (RABGAPs) are important factors for the coordination of cellular vesicle transport systems, and several TBC (TRE2-BUB2-CDC16) domain-containing RABGAPs are associated with autophagy. Employing C. elegans and human primary fibroblasts, we show that RAB3GAP1 and RAB3GAP2, which are components of the TBC domain-free RAB3GAP complex, influence protein aggregation and affect autophagy at basal and rapamycin-induced conditions...
2014: Autophagy
Peng Yao, Zhi-Bin Wang, Yuan-Yuan Ding, Jia-Ming Ma, Tao Hong, Shi-Nong Pan, Jin Zhang
The present study aimed to investigate the possible molecular mechanisms underlying the pathogenesis of metastatic osteosarcoma (OS), by examining the microarray expression profiles of normal samples, and metastatic and non‑metastatic OS samples. The GSE9508 gene expression profile was downloaded from the Gene Expression Omnibus database, which included 11 human metastatic OS samples, seven non‑metastatic OS samples and five normal samples. Pretreatment of the data was performed using the BioConductor package in R language, and the differentially expressed genes (DEGs) were identified by a t‑test...
March 2015: Molecular Medicine Reports
Dongjun Dai, Yunliang Wang, Jiaojiao Yuan, Xingyu Zhou, Danjie Jiang, Jinfeng Li, Yuzheng Zhang, Honglei Yin, Shiwei Duan
Schizophrenia (SCZ) is a severe complex psychiatric disorder that generates problems for the associated family and society and causes disability with regards to work for patients. The aim of the present study was to assess the contribution of 10 genetic polymorphisms to SCZ susceptibility. Meta-analyses were conducted using the data without a limitation for time or language. A total of 27 studies with 7 genes and 10 polymorphisms were selected for the meta-analyses. Two polymorphisms were found to be significantly associated with SCZ...
September 2014: Biomedical Reports
Antonio Rampino, Rosie May Walker, Helen Scott Torrance, Susan Maguire Anderson, Leonardo Fazio, Annabella Di Giorgio, Paolo Taurisano, Barbara Gelao, Raffaella Romano, Rita Masellis, Gianluca Ursini, Grazia Caforio, Giuseppe Blasi, J Kirsty Millar, David John Porteous, Pippa Ann Thomson, Alessandro Bertolino, Kathryn Louise Evans
Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function...
2014: PloS One
Yasuhito Watanabe, Konstantin Khodosevich, Hannah Monyer
Downregulation of the schizophrenia-associated gene DISC1 and its interacting protein FEZ1 positively regulates dendrite growth in young neurons. However, little is known about the mechanism that controls these molecules during neuronal development. Here, we identify several components of the ubiquitin proteasome system and the cell-cycle machinery that act upstream of FEZ1. We demonstrate that the ubiquitin ligase cell division cycle 20/anaphase-promoting complex (Cdc20/APC) controls dendrite growth by regulating the degradation of FEZ1...
April 24, 2014: Cell Reports
Marcos Rodrigo Alborghetti, Ariane da Silva Furlan, Júlio César da Silva, Maurício Luís Sforça, Rodrigo Vargas Honorato, Daniela Campos Granato, Deivid Lucas dos Santos Migueleti, Jorge L Neves, Paulo Sergio Lopes de Oliveira, Adriana Franco Paes-Leme, Ana Carolina de Mattos Zeri, Iris Concepcion Linares de Torriani, Jörg Kobarg
Cytoskeleton and protein trafficking processes, including vesicle transport to synapses, are key processes in neuronal differentiation and axon outgrowth. The human protein FEZ1 (fasciculation and elongation protein zeta 1 / UNC-76, in C. elegans), SCOCO (short coiled-coil protein / UNC-69) and kinesins (e.g. kinesin heavy chain / UNC116) are involved in these processes. Exploiting the feature of FEZ1 protein as a bivalent adapter of transport mediated by kinesins and FEZ1 protein interaction with SCOCO (proteins involved in the same path of axonal growth), we investigated the structural aspects of intermolecular interactions involved in this complex formation by NMR (Nuclear Magnetic Resonance), cross-linking coupled with mass spectrometry (MS), SAXS (Small Angle X-ray Scattering) and molecular modelling...
2013: PloS One
Caroline Behrens, Beyenech Binotti, Carla Schmidt, Carol V Robinson, John Jia En Chua, Karin Kühnel
The short coiled coil protein (SCOC) forms a complex with fasciculation and elongation protein zeta 1 (FEZ1). This complex is involved in autophagy regulation. We determined the crystal structure of the coiled coil domain of human SCOC at 2.7 Å resolution. SCOC forms a parallel left handed coiled coil dimer. We observed two distinct dimers in the crystal structure, which shows that SCOC is conformationally flexible. This plasticity is due to the high incidence of polar and charged residues at the core a/d-heptad positions...
2013: PloS One
John J E Chua, Reinhard Jahn, Dieter R Klopfenstein
Formation and normal function of neuronal synapses are intimately dependent on the delivery to and removal of biological materials from synapses by the intracellular transport machinery. Indeed, defects in intracellular transport contribute to the development and aggravation of neurodegenerative disorders. Despite its importance, regulatory mechanisms underlying this machinery remain poorly defined. We recently uncovered a phosphorylation-regulated mechanism that controls FEZ1-mediated Kinesin-1-based delivery of Stx1 into neuronal axons...
January 1, 2013: Worm
Y-Y Sun, Y Zhang, X-P Sun, T-Y Liu, Z-H Liu, G Chen, C-L Xia
AIMS: Fasciculation and elongation protein zeta-1 (FEZ1) is a critical regulator of dopaminergic neurone differentiation and dopamine release. However, to date, few studies evaluating the expression patterns of FEZ1 in Parkinson's disease (PD) have been reported. The aim of this study was to investigate the expression and cellular localization of FEZ1 in a rat model of PD and to explore the role of FEZ1 in PD pathogenesis. METHODS: Male Sprague-Dawley rats were randomly divided into two groups: a PD group and a sham group...
February 2014: Neuropathology and Applied Neurobiology
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