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https://www.readbyqxmd.com/read/29222813/reln-signaling-modulates-glioblastoma-growth-and-substrate-dependent-migration
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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...
May 24, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28507985/control-of-neuronal-migration-and-aggregation-by-reelin-signaling-in-the-developing-cerebral-cortex
#12
REVIEW
Yuki Hirota, Kazunori Nakajima
The mammalian cerebral neocortex has a well-organized laminar structure, achieved by the highly coordinated control of neuronal migration. During cortical development, excitatory neurons born near the lateral ventricle migrate radially to reach their final positions to form the cortical plate. During this process, dynamic changes are observed in the morphologies and migration modes, including multipolar migration, locomotion, and terminal translocation, of the newborn neurons. Disruption of these migration processes can result in neuronal disorders such as lissencephaly and periventricular heterotopia...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28484035/intersectin-1-is-a-component-of-the-reelin-pathway-to-regulate-neuronal-migration-and-synaptic-plasticity-in-the-hippocampus
#13
Burkhard Jakob, Gaga Kochlamazashvili, Maria Jäpel, Aziz Gauhar, Hans H Bock, Tanja Maritzen, Volker Haucke
Brain development and function depend on the directed and coordinated migration of neurons from proliferative zones to their final position. The secreted glycoprotein Reelin is an important factor directing neuronal migration. Loss of Reelin function results in the severe developmental disorder lissencephaly and is associated with neurological diseases in humans. Reelin signals via the lipoprotein receptors very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), but the exact mechanism by which these receptors control cellular function is poorly understood...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28433501/disrupted-in-schizophrenia-1-regulates-the-processing-of-reelin-in-the-perinatal-cortex
#14
Nicholas J Bradshaw, Svenja V Trossbach, Sabrina Köber, Susanne Walter, Ingrid Prikulis, Sascha Weggen, Carsten Korth
Disrupted in Schizophrenia 1 (DISC1) is a prominent gene in mental illness research, encoding a scaffold protein known to be of importance in the developing cerebral cortex. Reelin is a critical extracellular protein for development and lamination of the prenatal cortex and which has also been independently implicated in mental illness. Regulation of reelin activity occurs through processing by the metalloproteinases ADAMTS-4 and ADAMTS-5. Through cross-breeding of heterozygous transgenic DISC1 mice with heterozygous reeler mice, which have reduced reelin, pups heterozygous for both phenotypes were generated...
April 19, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28385118/neuroprotective-effect-of-melatonin-on-soluble-a%C3%AE-1-42-induced-cortical-neurodegeneration-via-reelin-dab1-signaling-pathway
#15
Chunli Hu, Pan Wang, Shuman Zhang, Lili Ren, Yiheng Lv, Rui Yin, Jing Bi
OBJECTIVE: Soluble Aβ1-42 oligomers play a vital role in the development and pathogenesis of Alzheimer's disease (AD). Melatonin could delay the progress of AD through multiple mechanisms. Reelin-Dab1 signaling plays an important role in AD, including neuronal function and synaptic plasticity. However, whether melatonin could exert its neuroprotective function against soluble Aβ1-42-induced neurotoxicity during AD development through regulating Reelin-Dab1 signaling remains poorly understood...
April 7, 2017: Neurological Research
https://www.readbyqxmd.com/read/28348420/reelin-expression-in-human-liver-of-patients-with-chronic-hepatitis-c-infection
#16
Simone Carotti, Giuseppe Perrone, Michelina Amato, Umberto Vespasiani Gentilucci, Daniela Righi, Maria Francesconi, Claudio Pellegrini, Francesca Zalfa, Maria Zingariello, Antonio Picardi, Andrea Onetti Muda, Sergio Morini
Reelin is a secreted extracellular glycoprotein that plays a critical role during brain development. Several studies have described Reelin expression in hepatic stellate cells of the human liver. In order to investigate the possible role of Reelin in the process of hepatic fibrogenesis, in this study we investigated Reelin expression in the liver tissue of patients infected with the Hepatitis C Virus (HCV). On this basis, Reelin expression was analysed by immunohistochemistry during liver biopsies of 81 patients with HCV-related chronic hepatitis...
March 17, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28298885/functional-roles-of-the-interaction-of-app-and-lipoprotein-receptors
#17
REVIEW
Theresa Pohlkamp, Catherine R Wasser, Joachim Herz
The biological fates of the key initiator of Alzheimer's disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28285824/clasp2-links-reelin-to-the-cytoskeleton-during-neocortical-development
#18
Gregory M Dillon, William A Tyler, Kerilyn C Omuro, John Kambouris, Camila Tyminski, Shawna Henry, Tarik F Haydar, Uwe Beffert, Angela Ho
The Reelin signaling pathway plays a crucial role in regulating neocortical development. However, little is known about how Reelin controls the cytoskeleton during neuronal migration. Here, we identify CLASP2 as a key cytoskeletal effector in the Reelin signaling pathway. We demonstrate that CLASP2 has distinct roles during neocortical development regulating neuron production and controlling neuron migration, polarity, and morphogenesis. We found downregulation of CLASP2 in migrating neurons leads to mislocalized cells in deeper cortical layers, abnormal positioning of the centrosome-Golgi complex, and aberrant length/orientation of the leading process...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28272509/optogenetic-control-of-the-dab1-signaling-pathway
#19
Liang Wang, Jonathan A Cooper
The Reelin-Dab1 signaling pathway regulates development of the mammalian brain, including neuron migrations in various brain regions, as well as learning and memory in adults. Extracellular Reelin binds to cell surface receptors and activates phosphorylation of the intracellular Dab1 protein. Dab1 is required for most effects of Reelin, but Dab1-independent pathways may contribute. Here we developed a single-component, photoactivatable Dab1 (opto-Dab1) by using the blue light-sensitive dimerization/oligomerization property of A...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28213441/secreted-metalloproteinase-adamts-3-inactivates-reelin
#20
Himari Ogino, Arisa Hisanaga, Takao Kohno, Yuta Kondo, Kyoko Okumura, Takana Kamei, Tempei Sato, Hiroshi Asahara, Hitomi Tsuiji, Masaki Fukata, Mitsuharu Hattori
The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, noninvasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro, but it remains controversial as to whether this effect occurs in vivo Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons...
March 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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