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https://www.readbyqxmd.com/read/27871939/cell-cell-communication-mediated-by-the-car-subgroup-of-immunoglobulin-cell-adhesion-molecules-in-health-and-disease
#1
REVIEW
Claudia Matthäus, Hanna Langhorst, Laura Schütz, René Jüttner, Fritz G Rathjen
The immunoglobulin superfamily represents a diverse set of cell-cell contact proteins and includes well-studied members such as NCAM1, DSCAM, L1 or the contactins which are strongly expressed in the nervous system. In this review we put our focus on the biological function of a less understood subgroup of Ig-like proteins composed of CAR (coxsackievirus and adenovirus receptor), CLMP (CAR-like membrane protein) and BT-IgSF (brain and testis specific immunoglobulin superfamily). The CAR-related proteins are type I transmembrane proteins containing an N-terminal variable (V-type) and a membrane proximal constant (C2-type) Ig domain in their extracellular region which are implicated in homotypic adhesion...
November 18, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27824329/de-novo-genic-mutations-among-a-chinese-autism-spectrum-disorder-cohort
#2
Tianyun Wang, Hui Guo, Bo Xiong, Holly A F Stessman, Huidan Wu, Bradley P Coe, Tychele N Turner, Yanling Liu, Wenjing Zhao, Kendra Hoekzema, Laura Vives, Lu Xia, Meina Tang, Jianjun Ou, Biyuan Chen, Yidong Shen, Guanglei Xun, Min Long, Janice Lin, Zev N Kronenberg, Yu Peng, Ting Bai, Honghui Li, Xiaoyan Ke, Zhengmao Hu, Jingping Zhao, Xiaobing Zou, Kun Xia, Evan E Eichler
Recurrent de novo (DN) and likely gene-disruptive (LGD) mutations contribute significantly to autism spectrum disorders (ASDs) but have been primarily investigated in European cohorts. Here, we sequence 189 risk genes in 1,543 Chinese ASD probands (1,045 from trios). We report an 11-fold increase in the odds of DN LGD mutations compared with expectation under an exome-wide neutral model of mutation. In aggregate, ∼4% of ASD patients carry a DN mutation in one of just 29 autism risk genes. The most prevalent gene for recurrent DN mutations is SCN2A (1...
November 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27666543/the-lncrna-landscape-of-breast-cancer-reveals-a-role-for-dscam-as1-in-breast-cancer-progression
#3
Yashar S Niknafs, Sumin Han, Teng Ma, Corey Speers, Chao Zhang, Kari Wilder-Romans, Matthew K Iyer, Sethuramasundaram Pitchiaya, Rohit Malik, Yasuyuki Hosono, John R Prensner, Anton Poliakov, Udit Singhal, Lanbo Xiao, Steven Kregel, Ronald F Siebenaler, Shuang G Zhao, Michael Uhl, Alexander Gawronski, Daniel F Hayes, Lori J Pierce, Xuhong Cao, Colin Collins, Rolf Backofen, Cenk S Sahinalp, James M Rae, Arul M Chinnaiyan, Felix Y Feng
Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1...
September 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27637097/replacing-the-pdz-interacting-c-termini-of-dscam-and-dscaml1-with-epitope-tags-causes-different-phenotypic-severity-in-different-cell-populations
#4
Andrew M Garrett, Abigail Ld Tadenev, Yuna T Hammond, Peter G Fuerst, Robert W Burgess
Different types of neurons in the retina are organized vertically into layers and horizontally in a mosaic pattern that helps ensure proper neural network formation and information processing throughout the visual field. The vertebrate Dscams (DSCAM and DSCAML1) are cell adhesion molecules that support the development of this organization by promoting self-avoidance at the level of cell types, promoting normal developmental cell death, and directing vertical neurite stratification. To understand the molecular interactions required for these activities, we tested the functional significance of the interaction between the C-terminus of the Dscams and multi-PDZ domain-containing scaffolding proteins in mouse...
2016: ELife
https://www.readbyqxmd.com/read/27421841/patient-mutations-of-the-intellectual-disability-gene-kdm5c-downregulate-netrin-g2-and-suppress-neurite-growth-in-neuro2a-cells
#5
Gengze Wei, Xinxian Deng, Saurabh Agarwal, Shigeki Iwase, Christine Disteche, Jun Xu
The X-linked lysine (K)-specific demethylase 5C (KDM5C) gene plays an important role in brain development and behavior. It encodes a histone demethylase that is involved in gene regulation in neuronal differentiation and morphogenesis. When mutated, it causes neuropsychiatric symptoms, such as intellectual disability, delayed language development, epilepsy, and impulsivity. To better understand how the patient mutations affect neuronal development, we expressed KDM5C mutants in Neuro2a cells, a mouse neuroblastoma cell line...
September 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27144534/retraction-bacteria-induced-dscam-isoforms-of-the-crustacean-pacifastacus-leniusculus
#6
Apiruck Watthanasurorot, Pikul Jiravanichpaisal, Haipeng Liu, Irene Söderhäll, Kenneth Söderhäll
No abstract text is available yet for this article.
May 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27080167/a-large-family-of-dscam-genes-with-tandemly-arrayed-5-cassettes-in-chelicerata
#7
Yuan Yue, Yijun Meng, Hongru Ma, Shouqing Hou, Guozheng Cao, Weiling Hong, Yang Shi, Pengjuan Guo, Baoping Liu, Feng Shi, Yun Yang, Yongfeng Jin
Drosophila Dscam1 (Down Syndrome Cell Adhesion Molecules) and vertebrate clustered protocadherins (Pcdhs) are two classic examples of the extraordinary isoform diversity from a single genomic locus. Dscam1 encodes 38,016 distinct isoforms via mutually exclusive splicing in D. melanogaster, while the vertebrate clustered Pcdhs utilize alternative promoters to generate isoform diversity. Here we reveal a shortened Dscam gene family with tandemly arrayed 5' cassettes in Chelicerata. These cassette repeats generally comprise two or four exons, corresponding to variable Immunoglobulin 7 (Ig7) or Ig7-8 domains of Drosophila Dscam1...
2016: Nature Communications
https://www.readbyqxmd.com/read/27046121/defective-angiogenesis-and-intraretinal-bleeding-in-mouse-models-with-disrupted-inner-retinal-lamination
#8
Aaron B Simmons, Morgan M Merrill, Justin C Reed, Michael R Deans, Malia M Edwards, Peter G Fuerst
PURPOSE: Abnormal retinal angiogenesis leads to visual impairment and blindness. Understanding how retinal vessels develop normally has dramatically improved treatments for people with retinal vasculopathies, but additional information about development is required. Abnormal neuron patterning in the outer retina has been shown to result in abnormal vessel development and blindness, for example, in people and mouse models with Crumbs homologue 1 (CRB1) mutations. In this study, we report and characterize a mouse model of inner retinal lamination disruption and bleeding, the Down syndrome cell adhesion molecule (Dscam) mutant, and test how neuron-neurite placement within the inner retina guides development of intraretinal vessels...
April 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/26991800/roles-of-the-laodelphax-striatellus-down-syndrome-cell-adhesion-molecule-in-rice-stripe-virus-infection-of-its-insect-vector
#9
F Zhang, Q Li, X Chen, Y Huo, H Guo, Z Song, F Cui, L Zhang, R Fang
The arthropod Down syndrome cell adhesion molecule (Dscam) mediates pathogen-specific recognition via an extensive protein isoform repertoire produced by alternative splicing. To date, most studies have focused on the subsequent pathogen-specific immune response, and few have investigated the entry into cells of viruses or endosymbionts. In the present study, we cloned and characterized the cDNA of Laodelphax striatellus Dscam (LsDscam) and investigated the function of LsDscam in rice stripe virus (RSV) infection and the influence on the endosymbiont Wolbachia...
August 2016: Insect Molecular Biology
https://www.readbyqxmd.com/read/26966010/overexpressed-down-syndrome-cell-adhesion-molecule-dscam-deregulates-p21-activated-kinase-pak-activity-in-an-in-vitro-neuronal-model-of-down-syndrome-consequences-on-cell-process-formation-and-extension
#10
Ramón Pérez-Núñez, Natalia Barraza, Arlek Gonzalez-Jamett, Ana Maria Cárdenas, Jean-Vianney Barnier, Pablo Caviedes
In humans, Down syndrome (DS) is caused by the presence of an extra copy of autosome 21. The most striking finding in DS patients is intellectual disability and the onset of Alzheimer's disease (AD)-like neuropathology in adulthood. Gene overdose is most likely to underlie both developmental impairments, as well as altered neuronal function in DS. Lately, the disruption of cellular signaling and regulatory pathways has been implicated in DS pathophysiology, and many of such pathways may represent common targets for diverse DS-related genes, which could in turn represent attractive therapeutical targets...
July 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/26930660/morphological-diversity-of-the-rod-spherule-a-study-of-serially-reconstructed-electron-micrographs
#11
Shuai Li, Joe Mitchell, Deidrie J Briggs, Jaime K Young, Samuel S Long, Peter G Fuerst
PURPOSE: Rod spherules are the site of the first synaptic contact in the retina's rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon...
2016: PloS One
https://www.readbyqxmd.com/read/26844831/dscam-proteins-direct-dendritic-targeting-through-adhesion
#12
Wael Tadros, Shuwa Xu, Orkun Akin, Caroline H Yi, Grace Ji-Eun Shin, S Sean Millard, S Lawrence Zipursky
Cell recognition molecules are key regulators of neural circuit assembly. The Dscam family of recognition molecules in Drosophila has been shown to regulate interactions between neurons through homophilic repulsion. This is exemplified by Dscam1 and Dscam2, which together repel dendrites of lamina neurons, L1 and L2, in the visual system. By contrast, here we show that Dscam2 directs dendritic targeting of another lamina neuron, L4, through homophilic adhesion. Through live imaging and genetic mosaics to dissect interactions between specific cells, we show that Dscam2 is required in L4 and its target cells for correct dendritic targeting...
February 3, 2016: Neuron
https://www.readbyqxmd.com/read/26844824/fly-dscams-can-also-help-you-find-the-right-partners
#13
COMMENT
Heike Blockus, Alain Chédotal
The modular reiterative pattern of the fly visual system makes it an ideal model to study axon guidance and synaptogenesis. In this issue of Neuron, Tadros et al. (2016) show that Dscam2/4 promote the anchoring of dendrites to their targets.
February 3, 2016: Neuron
https://www.readbyqxmd.com/read/26691152/novel-axon-projection-after-stress-and-degeneration-in-the-dscam-mutant-retina
#14
K A Fernandes, S J Bloomsburg, C J Miller, S A Billingslea, M M Merrill, R W Burgess, R T Libby, P G Fuerst
The Down syndrome cell adhesion molecule gene (Dscam) is required for normal dendrite patterning and promotes developmental cell death in the mouse retina. Loss-of-function studies indicate that Dscam is required for refinement of retinal ganglion cell (RGC) axons in the lateral geniculate nucleus, and in this study we report and describe a requirement for Dscam in the maintenance of RGC axon projections within the retina. Mouse Dscam loss of function phenotypes related to retinal ganglion cell axon outgrowth and targeting have not been previously reported, despite the abundance of axon phenotypes reported in Drosophila Dscam1 loss and gain of function models...
March 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/26683069/motor-hypertonia-and-lack-of-locomotor-coordination-in-mutant-mice-lacking-dscam
#15
Maxime Lemieux, Olivier D Laflamme, Louise Thiry, Antoine Boulanger-Piette, Jérôme Frenette, Frédéric Bretzner
Down syndrome cell adherence molecule (DSCAM) contributes to the normal establishment and maintenance of neural circuits. Whereas there is abundant literature regarding the role of DSCAM in the neural patterning of the mammalian retina, less is known about motor circuits. Recently, DSCAM mutation has been shown to impair bilateral motor coordination during respiration, thus causing death at birth. DSCAM mutants that survive through adulthood display a lack of locomotor endurance and coordination in the rotarod test, thus suggesting that the DSCAM mutation impairs motor control...
March 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/26655819/role-of-dscam-in-the-development-of-the-spinal-locomotor-and-sensorimotor-circuits
#16
Louise Thiry, Maxime Lemieux, Olivier D Laflamme, Frédéric Bretzner
Locomotion is controlled by spinal circuits that generate rhythm and coordinate left-right and flexor-extensor motoneuronal activities. The outputs of motoneurons and spinal interneuronal circuits are shaped by sensory feedback, relaying peripheral signals that are critical to the locomotor and postural control. Several studies in invertebrates and vertebrates have argued that the Down syndrome cell adhesion molecule (DSCAM) would play an important role in the normal development of neural circuits through cell spacing and targeting, axonal and dendritic branching, and synapse establishment and maintenance...
March 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/26644129/a-stripak-component-strip-regulates-neuronal-morphogenesis-by-affecting-microtubule-stability
#17
Chisako Sakuma, Misako Okumura, Tomoki Umehara, Masayuki Miura, Takahiro Chihara
During neural development, regulation of microtubule stability is essential for proper morphogenesis of neurons. Recently, the striatin-interacting phosphatase and kinase (STRIPAK) complex was revealed to be involved in diverse cellular processes. However, there is little evidence that STRIPAK components regulate microtubule dynamics, especially in vivo. Here, we show that one of the core STRIPAK components, Strip, is required for microtubule organization during neuronal morphogenesis. Knockdown of Strip causes a decrease in the level of acetylated α-tubulin in Drosophila S2 cells, suggesting that Strip influences the stability of microtubules...
December 8, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26621851/luminal-long-non-coding-rnas-regulated-by-estrogen-receptor-alpha-in-a-ligand-independent-manner-show-functional-roles-in-breast-cancer
#18
Valentina Miano, Giulio Ferrero, Stefania Reineri, Livia Caizzi, Laura Annaratone, Laura Ricci, Santina Cutrupi, Isabella Castellano, Francesca Cordero, Michele De Bortoli
Estrogen Receptor alpha (ERα) activation by estrogenic hormones induces luminal breast cancer cell proliferation. However, ERα plays also important hormone-independent functions to maintain breast tumor cells epithelial phenotype. We reported previously by RNA-Seq that in MCF-7 cells in absence of hormones ERα down-regulation changes the expression of several genes linked to cellular development, representing a specific subset of estrogen-induced genes. Here, we report regulation of long non-coding RNAs from the same experimental settings...
January 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/26554032/long-range-rna-pairings-contribute-to-mutually-exclusive-splicing
#19
Yuan Yue, Yun Yang, Lanzhi Dai, Guozheng Cao, Ran Chen, Weiling Hong, Baoping Liu, Yang Shi, Yijun Meng, Feng Shi, Mu Xiao, Yongfeng Jin
Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon cluster. Here, we reveal a molecular model for the regulation of the mutually exclusive splicing of the serpent pre-mRNA based on competition between upstream and downstream RNA pairings. Such dual RNA pairings confer fine tuning of the inclusion of alternative exons...
January 2016: RNA
https://www.readbyqxmd.com/read/26537380/somatic-and-germline-diversification-of-a-putative-immunoreceptor-within-one-phylum-dscam-in-arthropods
#20
REVIEW
Daniela Brites, Louis Du Pasquier
Arthropod Dscam, the homologue of the human Down Syndrome cell adhesion molecule, is a receptor used by the nervous and immune systems. Unlike in vertebrates, evolutionary pressure has selected and maintained a vast Dscam diversity of isoforms, known to specifying neuronal identity during the nervous system differentiation. This chapter examines the different modes of Dscam diversification in the context of arthropods' evolution and that of their immune system, where its role is controversial. In the single Dscam gene of insects and crustaceans, mutually exclusive alternative splicing affects three clusters of duplicated exons encoding the variable parts of the receptor...
2015: Results and Problems in Cell Differentiation
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