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https://www.readbyqxmd.com/read/28230174/a-hydrophobic-patch-surrounding-trp154-in-human-neuroserpin-controls-the-helix-f-dynamics-with-implications-in-inhibition-and-aggregation
#1
Mohammad Farhan Ali, Abhinav Kaushik, Charu Kapil, Dinesh Gupta, Mohamad Aman Jairajpuri
Neuroserpin (NS) mediated inhibition of tissue-type plasminogen activator (tPA) is important for brain development, synapse formation and memory. Aberrations in helix F and β-sheet A movement during inhibition can directly lead to epilepsy or dementia. Conserved W154 residue in a hydrophobic patch between helix F and β-sheet A is ideally placed to control their movement during inhibition. Molecular Dynamics (MD) simulation on wild type (WT) NS and its two variants (W154A and W154P) demonstrated partial deformation in helix F and conformational differences in strands 1A and 2A only in W154P...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228258/clonal-expansion-of-lgr5-positive-cells-from-mammalian-cochlea-and-high-purity-generation-of-sensory-hair-cells
#2
Will J McLean, Xiaolei Yin, Lin Lu, Danielle R Lenz, Dalton McLean, Robert Langer, Jeffrey M Karp, Albert S B Edge
Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228251/spatial-and-temporal-regulation-of-receptor-endocytosis-in-neuronal-dendrites-revealed-by-imaging-of-single-vesicle-formation
#3
Morgane Rosendale, Damien Jullié, Daniel Choquet, David Perrais
Endocytosis in neuronal dendrites is known to play a critical role in synaptic transmission and plasticity such as long-term depression (LTD). However, the inability to detect endocytosis directly in living neurons has hampered studies of its dynamics and regulation. Here, we visualized the formation of individual endocytic vesicles containing pHluorin-tagged receptors with high temporal resolution in the dendrites of cultured hippocampal neurons. We show that transferrin receptors (TfRs) are constitutively internalized at optically static clathrin-coated structures...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28220838/pan-neurexin-perturbation-results-in-compromised-synapse-stability-and-a-reduction-in-readily-releasable-synaptic-vesicle-pool-size
#4
Dylan P Quinn, Annette Kolar, Michael Wigerius, Rachel N Gomm-Kolisko, Hanine Atwi, James P Fawcett, Stefan R Krueger
Neurexins are a diverse family of cell adhesion molecules that localize to presynaptic specializations of CNS neurons. Heterologous expression of neurexins in non-neuronal cells leads to the recruitment of postsynaptic proteins in contacting dendrites of co-cultured neurons, implicating neurexins in synapse formation. However, isoform-specific knockouts of either all α- or all β-neurexins show defects in synaptic transmission but an unaltered density of glutamatergic synapses, a finding that argues against an essential function of neurexins in synaptogenesis...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219683/the-c1q-complement-family-of-synaptic-organizers-not-just-complementary
#5
REVIEW
Michisuke Yuzaki
Molecules that regulate formation, differentiation, and maintenance of synapses are called synaptic organizers. Recently, various 'C1q family' proteins have been shown to be released from neurons, and serve as a new class of synaptic organizers. Cbln1 and C1ql1 proteins regulate the formation and maintenance of parallel fiber-Purkinje cell and climbing fiber-Purkinje cell synapses, respectively, in the cerebellum. Cbln1 also modulates the function of postsynaptic delta2 glutamate receptors to regulate synaptic plasticity...
February 17, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28218426/dkk3-attenuates-the-cytotoxic-effect-of-natural-killer-cells-on-cd133-gastric-cancer-cells
#6
Pu Xia, Xiao-Yan Xu
Cancer stem cell (CSCs) has started a new era in cancer research. CD133 is a widely used marker for identification of CSCs. More and more studies showed that NK cells preferentially target cancer stem-like cells. However, the deeper mechanism of the susceptibility of cancer stem cells to NK cells remains unclear. In this study, we isolated CD133 positive population of a gastric cancer cell line, BGC823 cells, and cultured with NK cells. We found that CD133 could efficiently active NK cells in an NKG2D-dependent manner...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28214564/downregulation-of-gna13-erk-network-in-prefrontal-cortex-of-schizophrenia-brain-identified-by-combined-focused-and-targeted-quantitative-proteomics
#7
Mio Hirayama-Kurogi, Yohei Takizawa, Yasuto Kunii, Junya Matsumoto, Akira Wada, Mizuki Hino, Hiroyasu Akatsu, Yoshio Hashizume, Sakon Yamamoto, Takeshi Kondo, Shingo Ito, Masanori Tachikawa, Shin-Ichi Niwa, Hirooki Yabe, Tetsuya Terasaki, Mitsutoshi Setou, Sumio Ohtsuki
: Schizophrenia is a disabling mental illness associated with dysfunction of the prefrontal cortex, which affects cognition and emotion. The purpose of the present study was to identify altered molecular networks in the prefrontal cortex of schizophrenia patients by comparing protein expression levels in autopsied brains of patients and controls, using a combination of targeted and focused quantitative proteomics. We selected 125 molecules possibly related to schizophrenia for quantification by knowledge-based targeted proteomics...
February 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#8
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28213516/rapid-regulation-of-sialidase-activity-in-response-to-neural-activity-and-sialic-acid-removal-during-memory-processing-in-rat-hippocampus
#9
Akira Minami, Yuko Meguro, Sayaka Ishibashi, Ami Ishii, Mako Shiratori, Saki Sai, Yuuki Horii, Hirotaka Shimizu, Hokuto Fukumoto, Sumika Shinba, Risa Taguchi, Tadanobu Takahashi, Tadamune Otsubo, Kiyoshi Ikeda, Takashi Suzuki
Sialidase cleaves sialic acids on the extracellular cell surface as well as inside the cell, and is necessary for normal long-term potentiation (LTP) at MF-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4MU-Neu5Ac or X-Neu5Ac and FRV LB was increased by high K(+)-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDARs or NMDARs...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213440/muscle-yap-is-a-regulator-of-neuromuscular-junction-formation-and-regeneration
#10
Kai Zhao, Chengyong Shen, Yisheng Lu, Zhihui Huang, Lei Li, Christopher D Rand, Jinxiu Pan, Xiang-Dong Sun, Zhibing Tan, Hongsheng Wang, Guanglin Xing, Yu Cao, Guoqing Hu, Jiliang Zhou, Wen-Cheng Xiong, Lin Mei
Yes-associated protein (Yap) is a major effector of the Hippo pathway that regulates cell proliferation and differentiation during development and restricts tissue growth in adult animals. However, its role in synapse formation remains poorly understood. In this study, we characterized Yap's role in the formation of neuromuscular junction (NMJ). In HSA-Yap(-/-) mice where Yap was mutated specifically in muscle cells, AChR clusters were smaller and were distributed in a broader region in the middle of muscle fibers, suggesting that muscle Yap is necessary for the size and location of AChR clusters...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28211900/amyloid-%C3%AE-oligomers-interact-with-neurexin-and-diminish-neurexin-mediated-excitatory-presynaptic-organization
#11
Yusuke Naito, Yuko Tanabe, Alfred Kihoon Lee, Edith Hamel, Hideto Takahashi
Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210208/promoter-specific-expression-and-genomic-structure-of-iglon-family-genes-in-mouse
#12
Taavi Vanaveski, Katyayani Singh, Jane Narvik, Kattri-Liis Eskla, Tanel Visnapuu, Indrek Heinla, Mohan Jayaram, Jürgen Innos, Kersti Lilleväli, Mari-Anne Philips, Eero Vasar
IgLON family is composed of five genes: Lsamp, Ntm, Opcml, Negr1, and Iglon5; encoding for five highly homologous neural adhesion proteins that regulate neurite outgrowth and synapse formation. In the current study we performed in silico analysis revealing that Ntm and Opcml display similar genomic structure as previously reported for Lsamp, characterized by two alternative promotors 1a and 1b. Negr1 and Iglon5 transcripts have uniform 5' region, suggesting single promoter. Iglon5, the recently characterized family member, shares high level of conservation and structural qualities characteristic to IgLON family such as N-terminal signal peptide, three Ig domains, and GPI anchor binding site...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28209780/microtubule-associated-protein-4-map4-controls-nanovesicle-dynamics-and-t-cell-activation
#13
Eugenio Bustos-Morán, Noelia Blas-Rus, Noa Martin-Cófreces, Francisco Sánchez-Madrid
The Immune Synapse (IS) is a specialized structure formed at the contact area between T lymphocytes and antigen-presenting cells (APC), essential for the adaptive immune response. Proper T cell activation requires its polarization towards the APC, which is highly dependent on the tubulin cytoskeleton. Microtubule associated protein-4 (MAP4) is a microtubule (MT)-stabilizing protein that controls MTs in physiological processes such as cell division, migration, vesicular transport or primary cilia formation. In this study, we have assessed the role of MAP4 in T cell activation...
February 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28205605/the-role-of-the-rna-demethylase-fto-fat-mass-and-obesity-associated-and-mrna-methylation-in-hippocampal-memory-formation
#14
Brandon J Walters, Valentina Mercaldo, Colleen J Gillon, Matthew Yip, Rachael L Neve, Frederick M Boyce, Paul W Frankland, Sheena A Josselyn
The formation of long-lasting memories requires coordinated changes in gene expression and protein synthesis (Davis and Squire, 1984; Duvarci et al, 2008; Hernandez and Abel, 2008). Although many studies implicate DNA modifications (DNA methylation, histone modifications) in memory formation, the contributions of RNA modifications remain largely unexplored. Here, we investigated the role of mRNA methylation in hippocampal-dependent memory formation in mice. RNA modifications are highly dynamic and readily reversible (Jia et al, 2013)...
February 16, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28202613/the-activating-human-nk-cell-receptor-kir2ds2-recognizes-a-%C3%AE-2-microglobulin-independent-ligand-on-cancer-cells
#15
Lavanya Thiruchelvam-Kyle, Sigurd E Hoelsbrekken, Per C Saether, Elisabeth Gyllensten Bjørnsen, Daniela Pende, Sigbjørn Fossum, Michael R Daws, Erik Dissen
The functions of activating members of the killer cell Ig-like receptor (KIR) family are not fully understood, as the ligands for these receptors are largely unidentified. In this study, we report that KIR2DS2 reporter cells recognize a ligand expressed by cancer cell lines. All cancer targets recognized by KIR2DS2 were also recognized by KIR2DL2 and KIR2DL3 reporters. Trogocytosis of membrane proteins from the cancer targets was observed with responding reporter cells, indicating the formation of KIR2DS2 ligand-specific immunological synapses...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28199019/the-role-of-drebrin-in-neurons
#16
REVIEW
Tomoaki Shirao, Kenji Hanamura, Noriko Koganezawa, Yuta Ishizuka, Hiroyuki Yamazaki, Yuko Sekino
Drebrin is an actin-binding protein that changes the helical pitch of actin filaments (F-actin), and drebrin-decorated F-actin shows slow treadmilling and decreased rate of depolymerization. Moreover, the characteristic morphology of drebrin-decorated F-actin enables it to respond differently to the same signals from other actin cytoskeletons. Drebrin consists of two major isoforms, drebrin E and drebrin A. In the developing brain, drebrin E appears in migrating neurons and accumulates in the growth cones of axons and dendrites...
February 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28197078/redundant-postsynaptic-functions-of-syncams-1-3-during-synapse-formation
#17
Daniel K Fowler, James H Peters, Carly Williams, Philip Washbourne
Investigating the roles of synaptogenic adhesion molecules during synapse formation has proven challenging, often due to compensatory functions between additional family members. The synaptic cell adhesion molecules 1-3 (SynCAM1-3) are expressed both pre- and postsynaptically, share highly homologous domains and are synaptogenic when ectopically presented to neurons; yet their endogenous functions during synaptogenesis are unclear. Here we report that SynCAM1-3 are functionally redundant and collectively necessary for synapse formation in cultured hippocampal neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28194092/paradoxes-of-the-ephb1-receptor-in-malignant-brain-tumors
#18
REVIEW
Wenqiang Wei, Hongju Wang, Shaoping Ji
Eph receptors are a subfamily of receptor tyrosine kinases. Eph receptor-mediated forward and ephrin ligand-mediated reverse signalings are termed bidirectional signaling. Increasing evidence shows that Eph/ephrin signaling regulates cell migration, adhesion, morphological changes, differentiation, proliferation and survival through cell-cell communication. Some recent studies have started to implicate Eph/ephrin signaling in tumorigenesis, metastasis, and angiogenesis. Previous studies have shown that EphB1 receptor and its ephrin ligands are expressed in the central nervous system...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28193459/epileptiform-activity-and-behavioral-arrests-in-mice-overexpressing-the-calcium-channel-subunit-%C3%AE-2%C3%AE-1
#19
Leonardo C Faria, Feng Gu, Isabel Parada, Ben Barres, Z David Luo, David A Prince
: The alpha2delta-1 subunit (α2δ-1) of voltage-gated calcium channels is a receptor for astrocyte-secreted thrombospondins that promote developmental synaptogenesis.Alpha2delta-1 receptors are upregulated in models of injury-induced peripheral pain and epileptogenic neocortical trauma associated with an enhancement of excitatory synaptic connectivity. These results lead to the hypothesis that overexpression of α2δ-1 alone in neocortex of uninjured transgenic (TG) mice might result in increased excitatory connectivity and consequent cortical hyperexcitability and epileptiform activity...
February 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28185854/a-dual-role-for-the-rhogef-ephexin5-in-regulation-of-dendritic-spine-outgrowth
#20
A M Hamilton, J T Lambert, L K Parajuli, O Vivas, D K Park, I S Stein, J N Jahncke, M E Greenberg, S S Margolis, K Zito
The outgrowth of new dendritic spines is closely linked to the formation of new synapses, and is thought to be a vital component of the experience-dependent circuit plasticity that supports learning. Here, we examined the role of the RhoGEF Ephexin5 in driving activity-dependent spine outgrowth. We found that reducing Ephexin5 levels increased spine outgrowth, and increasing Ephexin5 levels decreased spine outgrowth in a GEF-dependent manner, suggesting that Ephexin5 acts as an inhibitor of spine outgrowth...
February 6, 2017: Molecular and Cellular Neurosciences
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