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https://www.readbyqxmd.com/read/29661967/detachment-of-chain-forming-neuroblasts-by-fyn-mediated-control-of-cell-cell-adhesion-in-the-postnatal-brain
#1
Kazuma Fujikake, Masato Sawada, Takao Hikita, Yayoi Seto, Naoko Kaneko, Vicente Herranz-Pérez, Natsuki Dohi, Natsumi Homma, Satoshi Osaga, Yuchio Yanagawa, Toshihiro Akaike, Jose Manuel García-Verdugo, Mitsuharu Hattori, Kazuya Sobue, Kazunobu Sawamoto
In the rodent olfactory system, neuroblasts produced in the ventricular-subventricular zone of the postnatal brain migrate tangentially in chain-like cell aggregates toward the olfactory bulb (OB) through the rostral migratory stream (RMS). After reaching the OB, the chains are dissociated and the neuroblasts migrate individually and radially toward their final destination. The cellular and molecular mechanisms controlling cell-cell adhesion during this detachment remain unclear. Here we report that Fyn, a non-receptor tyrosine kinase, regulates the detachment of neuroblasts from chains in the male and female mouse OB...
April 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29590626/dcc-mediated-dab1-phosphorylation-participates-in-the-multipolar-to-bipolar-transition-of-migrating-neurons
#2
Jian-Hua Zhang, Yi-Fei Zhao, Xiao-Xiao He, Yang Zhao, Zi-Xuan He, Lei Zhang, Ying Huang, Yu-Bing Wang, Ling Hu, Lin Liu, Hua-Li Yu, Jia-Hui Xu, Ming-Ming Lai, Dong-Dong Zhao, Lei Cui, Wei-Xiang Guo, Wen-Cheng Xiong, Yu-Qiang Ding, Xiao-Juan Zhu
Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29581187/rbm4-modulates-radial-migration-via-alternative-splicing-of-dab1-during-cortex-development
#3
Dhananjaya D, Kuan-Yang Hung, Woan-Yuh Tarn
The RNA-binding motif 4 (RBM4) protein participates in cell differentiation via its role in regulating the expression of or tissue-specific or developmentally regulated mRNA splice isoforms. RBM4 is expressed in embryonic brain during development; it is initially enriched in the ventricular zone/subventricular zone and subsequently distributed throughout the cortical cortex. Rbm4a knockout brain exhibited delayed migration of late-born neurons. Using in utero electroporation, we confirmed that knockdown of RBM4 impaired cortical neuronal migration...
March 26, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29536172/developmental-abnormality-contributes-to-cortex-dependent-motor-impairments-and-higher-intracortical-current-requirement-in-the-reeler-homozygous-mutants
#4
Mariko Nishibe, Yu Katsuyama, Toshihide Yamashita
The motor deficit of the reeler mutants has largely been considered cerebellum related, and the developmental consequences of the cortex on reeler motor behavior have not been examined. We herein showed that there is a behavioral consequence to reeler mutation in models examined at cortex-dependent bimanual tasks that require forepaw dexterity. Using intracortical microstimulation, we found the forelimb representation in the motor cortex was significantly reduced in the reeler. The reeler cortex required a significantly higher current to evoke skeletal muscle movements, suggesting the cortical trans-synaptic propagation is disrupted...
March 13, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29518789/genome-wide-dna-methylation-profiles-of-phlegm-dampness-constitution
#5
Haiqiang Yao, Shanlan Mo, Ji Wang, Yingshuai Li, Chong-Zhi Wang, Jin-Yi Wan, Zengliang Zhang, Yu Chen, Ranran Sun, Chun-Su Yuan, Xin Liu, Lingru Li, Qi Wang
BACKGROUND/AIMS: Metabolic diseases are leading health concerns in today's global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. METHODS: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs)...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29512697/ephrin%C3%A2-b3-modulates-hippocampal-neurogenesis-and-the-reelin-signaling-pathway-in-a-pilocarpine%C3%A2-induced-model-of-epilepsy
#6
Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng
Ephrin‑B3 is important in the regulation of cell proliferation, differentiation and migration via cell‑cell contact, and can activate the reelin pathway during brain development. However, the effect of ephrin‑B3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrin‑B3 in pilocarpine‑induced status epilepticus (SE) rats was investigated. SYBR Green‑based reverse transcription‑quantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrin‑B3 and reelin pathway proteins...
March 7, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29472232/genome-wide-association-and-functional-studies-identify-scml4-and-thsd7a-as-novel-susceptibility-genes-for-coronary-artery-disease
#7
Yang Li, Dao Wen Wang, Yundai Chen, Can Chen, Jian Guo, Shu Zhang, Zhijun Sun, Hu Ding, Yan Yao, Lei Zhou, Ke Xu, Chun Song, Fan Yang, Bin Zhao, Han Yan, Wen-Jing Wang, Chong Wu, Xiangfeng Lu, Xueli Yang, Jie Dong, Guyan Zheng, Shuhan Tian, Yanjun Cui, Lijuan Jin, Gangqiong Liu, Hanbin Cui, Shenghuang Wang, Feng Jiang, Changhua Wang, Jeanette Erdmann, Linyao Zeng, Shian Huang, Jianfeng Zhong, Yuehua Ma, Wenjiang Chen, Jianli Sun, Wei Lei, Shenghan Chen, Shaoqi Rao, Dongfeng Gu, Heribert Schunkert, Xiao-Li Tian
OBJECTIVE: The genetic contribution to coronary artery disease (CAD) remains largely unclear. We combined genetic screening with functional characterizations to identify novel loci and candidate genes for CAD. APPROACH AND RESULTS: We performed genome-wide screening followed by multicenter validation in 8 cohorts consisting of 21 828 participants of Han ethnicity and identified 3 novel intragenic SNPs, rs9486729 ( SCML4 ; odds ratio, 1.25; 95% CI, 1.17-1.34; P =3...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29470947/small-and-large-intestine-express-a-truncated-dab1-isoform-that-assembles-in-cell-cell-junctions-and-co-localizes-with-proteins-involved-in-endocytosis
#8
María D Vázquez-Carretero, Pablo García-Miranda, María S Balda, Karl Matter, María J Peral, Anunciación A Ilundain
Disabled-1 (Dab1) is an essential intracellular adaptor protein in the reelin pathway. Our previous studies in mice intestine showed that Dab1 transmits the reelin signal to cytosolic signalling pathways. Here, we determine the Dab1 isoform expressed in rodent small and large intestine, its subcellular location and co-localization with clathrin, caveolin-1 and N-Wasp. PCR and sequencing analysis reveal that rodent small and large intestine express a Dab1 isoform that misses three (Y198 , Y200 and Y220 ) of the five tyrosine phosphorylation sites present in brain Dab1 isoform (canonical) and contains nuclear localization and export signals...
February 19, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29361558/rbx2-maintains-final-retinal-cell-position-in-a-dab1-dependent-and-independent-fashion
#9
Corinne L Fairchild, Keiko Hino, Jisoo S Han, Adam M Miltner, Gabriel Peinado Allina, Caileigh E Brown, Marie E Burns, Anna La Torre, Sergi Simó
The laminated structure of the retina is fundamental for the organization of the synaptic circuitry that translates light input into patterns of action potentials. However, the molecular mechanisms underlying cell migration and layering of the retina are poorly understood. Here, we show that RBX2, a core component of the E3 ubiquitin ligase CRL5, is essential for retinal layering and function. RBX2 regulates the final cell position of rod bipolar cells, cone photoreceptors and Muller glia. Our data indicate that sustained RELN/DAB1 signaling, triggered by depletion of RBX2 or SOCS7 - a CRL5 substrate adaptor known to recruit DAB1 - causes rod bipolar cell misposition...
February 2, 2018: Development
https://www.readbyqxmd.com/read/29222813/reln-signaling-modulates-glioblastoma-growth-and-substrate-dependent-migration
#10
Markus Schulze, Christ Violonchi, Stefan Swoboda, Tobias Welz, Eugen Kerkhoff, Sabine Hoja, Susanne Brüggemann, Johann Simbürger, Jörg Reinders, Markus J Riemenschneider
Glioblastoma (GBM) represents the most common and most malignant type of primary brain tumor and significantly contributes to cancer morbidity and mortality. Invasion into the healthy brain parenchyma is a major feature of glioblastoma aggressiveness. Reelin (RELN) is a large secreted extracellular matrix glycoprotein that regulates neuronal migration and positioning in the developing brain and sustains functionality in the adult brain. We here show that both RELN and its main downstream effector DAB1 are silenced in glioblastoma as compared to non-neoplastic tissue and mRNA expression is inversely correlated with malignancy grade...
December 8, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29219038/duplication-and-variation-in-the-major-histocompatibility-complex-genes-in-blakiston-s-fish-owl-bubo-blakistoni
#11
Keita Omote, Tetsuo I Kohyama, Chizuko Nishida, Keisuke Saito, Satoshi Fujimoto, Ryuichi Masuda
The major histocompatibility complex (MHC) includes many genes that are essential for the adaptive immune system, and variation in the antigen binding site (ABS) is related to resistance against pathogens. In the present study, quantitative real-time PCR indicated a larger number of MHC gene copies in the endangered population of Blakiston's fish owl (Bubo blakistoni) than in five other owl species, and massively parallel pyrosequencing detected more MHC class IIβ per individual alleles in B. blakistoni than in the other species...
December 2017: Zoological Science
https://www.readbyqxmd.com/read/29212900/genome-wide-gene-potassium-interaction-analyses-on-blood-pressure-the-gensalt-study-genetic-epidemiology-network-of-salt-sensitivity
#12
Changwei Li, Jiang He, Jing Chen, Jinying Zhao, Dongfeng Gu, James E Hixson, Dabeeru C Rao, Cashell E Jaquish, Treva K Rice, Yun Ju Sung, Tanika N Kelly
BACKGROUND: Gene-environmental interaction analysis can identify novel genetic factors for blood pressure (BP). We performed genome-wide analyses to identify genomic loci that interact with potassium to influence BP using single-marker (1 and 2 df joint tests) and gene-based tests among Chinese participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). METHODS AND RESULTS: Among 1876 GenSalt participants, the average of 3 urine samples was used to estimate potassium excretion...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29049379/mathematical-model-of-early-reelin-induced-src-family-kinase-mediated-signaling
#13
Helge Hass, Friederike Kipkeew, Aziz Gauhar, Elisabeth Bouché, Petra May, Jens Timmer, Hans H Bock
Reelin is a large glycoprotein with a dual role in the mammalian brain. It regulates the positioning and differentiation of postmitotic neurons during brain development and modulates neurotransmission and memory formation in the adult brain. Alterations in the Reelin signaling pathway have been described in different psychiatric disorders. Reelin mainly signals by binding to the lipoprotein receptors Vldlr and ApoER2, which induces tyrosine phosphorylation of the adaptor protein Dab1 mediated by Src family kinases (SFKs)...
2017: PloS One
https://www.readbyqxmd.com/read/28968791/alternative-splicing-of-disabled-1-controls-multipolar-to-bipolar-transition-of-migrating-neurons-in-the-neocortex
#14
Bin Zhang, Weiwei Wang, Zhenjie Zhang, Yaling Hu, Fan Meng, Fan Wang, Huifang Lou, Liya Zhu, Roseline Godbout, Shumin Duan, Zhihua Gao
Multipolar-to-bipolar transition (MBT) is crucial for the neuronal migration and positioning in the neocortex. Reelin-Disabled-1 (Dab1) signaling plays a pivotal role in neuronal migration, yet how Dab1 coordinatively regulates downstream molecules to affect MBT remains unclear. We have previously found that alternative splicing produces multiple Dab1 isoforms with different tyrosine motifs and differential ability to recruit downstream effectors. Here, we report that splicing of Dab1 exons 7 and 8 and 9bc dynamically regulates the inclusion and activities of Dab1 tyrosine motifs in the neocortex...
August 22, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28966264/regulatory-mechanisms-and-physiological-significance-of-reelin-function
#15
REVIEW
Takao Kohno
Reelin is a large secreted glycoprotein that regulates embryonic neuronal lamination and adult synaptic function. Secreted Reelin binds to lipoprotein receptors expressed on neurons. The Reelin-receptor interaction induces phosphorylation of an intracellular adaptor protein Dab1, which is required for normal embryonic brain development and adult brain functions. It has been suggested that Reelin hypofunction plays a role in the pathogenesis of several neuropsychiatric diseases, such as schizophrenia, autism, and Alzheimer's disease...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28945921/dab1-contributes-differently-to-the-morphogenesis-of-the-hippocampal-subdivisions
#16
Marissa Blume, Fuduki Inoguchi, Taku Sugiyama, Yuji Owada, Noriko Osumi, Yoshinari Aimi, Kosuke Taki, Yu Katsuyama
The hippocampal formation (HF) is morphologically and functionally distinguishable into the subdivisions, such as the dentate gyrus (DG), subiculum, and Ammon's horn. The Ammon's horn is further divided into the CA (Cornu Ammonis)1, CA2, and CA3. The Reelin-Dab1 signal is essential for the morphogenesis of the mammalian brain. In the neocortex of Reelin-Dab1 signal mutants the laminar pattern of the neurons is disrupted along the radial axis. Morphological abnormalities in the HF of the Reelin-Dab1 mutants were known, but how these abnormalities appear during development had not been extensively studied...
September 25, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28887403/the-functions-of-reelin-in-membrane-trafficking-and-cytoskeletal-dynamics-implications-for-neuronal-migration-polarization-and-differentiation
#17
REVIEW
Jessica Santana, María-Paz Marzolo
Reelin is a large extracellular matrix protein with relevant roles in mammalian central nervous system including neurogenesis, neuronal polarization and migration during development; and synaptic plasticity with its implications in learning and memory, in the adult. Dysfunctions in reelin signaling are associated with brain lamination defects such as lissencephaly, but also with neuropsychiatric diseases like autism, schizophrenia and depression as well with neurodegeneration. Reelin signaling involves a core pathway that activates upon reelin binding to its receptors, particularly ApoER2 (apolipoprotein E receptor 2)/LRP8 (low-density lipoprotein receptor-related protein 8) and very low-density lipoprotein receptor, followed by Src/Fyn-mediated phosphorylation of the adaptor protein Dab1 (Disabled-1)...
September 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28686858/a-pentanucleotide-atttc-repeat-insertion-in-the-non-coding-region-of-dab1-mapping-to-sca37-causes-spinocerebellar-ataxia
#18
Ana I Seixas, Joana R Loureiro, Cristina Costa, Andrés Ordóñez-Ugalde, Hugo Marcelino, Cláudia L Oliveira, José L Loureiro, Ashutosh Dhingra, Eva Brandão, Vitor T Cruz, Angela Timóteo, Beatriz Quintáns, Guy A Rouleau, Patrizia Rizzu, Ángel Carracedo, José Bessa, Peter Heutink, Jorge Sequeiros, Maria J Sobrido, Paula Coutinho, Isabel Silveira
Advances in human genetics in recent years have largely been driven by next-generation sequencing (NGS); however, the discovery of disease-related gene mutations has been biased toward the exome because the large and very repetitive regions that characterize the non-coding genome remain difficult to reach by that technology. For autosomal-dominant spinocerebellar ataxias (SCAs), 28 genes have been identified, but only five SCAs originate from non-coding mutations. Over half of SCA-affected families, however, remain without a genetic diagnosis...
July 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28676854/dab1-contributes-to-angiotensin-ii-induced-apoptosis-via-p38-signaling-pathway-in-podocytes
#19
Zhao Gao, Xinghua Chen, Kai Zhu, Ping Zeng, Guohua Ding
Numerous studies have found that angiotensin II (Ang II) participates in podocyte apoptosis and exacerbates progression of end-stage kidney disease (ESKD). However, its underlying mechanism remains largely unexplored. As a homolog of Drosophila disabled (Dab) protein, Dab1 plays a vital role in cytoskeleton, neuronal migration, and proliferation. In the present study, our data revealed that Ang II-infused rats developed hypertension, proteinuria, and podocyte injury accompanied by Dab1 phosphorylation and increased reelin expression in kidney...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28544613/qtl-and-systems-genetics-analysis-of-mouse-grooming-and-behavioral-responses-to-novelty-in-an-open-field
#20
A Delprato, M-P Algéo, B Bonheur, J A Bubier, L Lu, R W Williams, E J Chesler, W E Crusio
The open field is a classic test used to assess exploratory behavior, anxiety and locomotor activity in rodents. Here, we mapped quantitative trait loci (QTLs) underlying behaviors displayed in an open field, using a panel of 53 BXD recombinant inbred mouse strains with deep replication (10 per strain and sex). The use of these strains permits the integration and comparison of data obtained in different laboratories, and also offers the possibility to study trait covariance by exploiting powerful bioinformatics tools and resources...
November 2017: Genes, Brain, and Behavior
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