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https://www.readbyqxmd.com/read/27908790/mpp-inhibits-mglur1-5-mediated-long-term-depression-in-mouse-hippocampus-by-calpain-activation
#1
Junyao Li, Hui Chen, Shengbing Wu, Yuefa Cheng, Qinglin Li, Jing Wang, Guoqi Zhu
Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of neurotoxin, 1-methyl-4-phenylpyridinium (MPP(+)), on metabotropic glutamate receptor 1/5 agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced hippocampal synaptic plasticity, and MPP(+) incubation blocked DHPG-induced hippocampal long-term depression (LTD) in Schaffer collateral-CA1 synapses...
November 28, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27907191/trio-a-rho-family-gef-interacts-with-the-presynaptic-active-zone-proteins-piccolo-and-bassoon
#2
Ryan T Terry-Lorenzo, Viviana I Torres, Dhananjay Wagh, Jose Galaz, Selene K Swanson, Laurence Florens, Michael P Washburn, Clarissa L Waites, Eckart D Gundelfinger, Richard J Reimer, Craig C Garner
Synaptic vesicles (SVs) fuse with the plasma membrane at a precise location called the presynaptic active zone (AZ). This fusion is coordinated by proteins embedded within a cytoskeletal matrix assembled at the AZ (CAZ). In the present study, we have identified a novel binding partner for the CAZ proteins Piccolo and Bassoon. This interacting protein, Trio, is a member of the Dbl family of guanine nucleotide exchange factors (GEFs) known to regulate the dynamic assembly of actin and growth factor dependent axon guidance and synaptic growth...
2016: PloS One
https://www.readbyqxmd.com/read/27881663/periodic-actin-structures-in-neuronal-axons-are-required-to-maintain-microtubules
#3
Yue Qu, Ines Hahn, Stephen Webb, Simon P Pearce, Andreas Prokop
Axons are the cable-like neuronal processes wiring the nervous system. They contain parallel bundles of microtubules as structural backbones, surrounded by regularly-spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an evolutionarily-conserved, ubiquitous, highly-ordered feature of axons, the function of PMS is unknown. Here we studied PMS abundance, organisation and function, combining versatile Drosophila genetics with super-resolution microscopy and various functional readouts...
November 23, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27863449/il6-mediated-inflammatory-loop-reprograms-normal-to-emt-metastatic-cscs-in-pre-neoplastic-liver-of-tgf%C3%AE-deficient-%C3%AE-2sp-mice
#4
Abhisek Mitra, Jun Yan, Xueqing Xia, Shouhao Zhou, Jian Chen, Lopa Mishra, Shulin Li
Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related deaths world-wide with poor survival rate. As many as 40% of HCCs are clonal, with alteration of key tumor suppressor pathways in stem cells is the primary cause of HCC initiation. However, mechanisms that generate metastatic stem cells in pre-neoplastic liver tissue are not well understood. We hypothesized that chronic inflammation is a major driver of the transformation of genetically defective liver stem cells (LSCs) into highly metastatic liver cancer cells in premalignant liver tissue...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27857681/early-cytoskeletal-protein-modifications-precede-overt-structural-degeneration-in-the-dba-2j-mouse-model-of-glaucoma
#5
Gina N Wilson, Matthew A Smith, Denise M Inman, Christine M Dengler-Crish, Samuel D Crish
Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins, and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma. Using anterograde tract tracing of the retinal projection, we assessed major cytoskeletal and transported elements as a function of transport integrity in different stages of pathological progression...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27856737/global-transformation-of-erythrocyte-properties-via-engagement-of-an-sh2-like-sequence-in-band-3
#6
Estela Puchulu-Campanella, Francesco M Turrini, Yen-Hsing Li, Philip S Low
Src homology 2 (SH2) domains are composed of weakly conserved sequences of ∼100 aa that bind phosphotyrosines in signaling proteins and thereby mediate intra- and intermolecular protein-protein interactions. In exploring the mechanism whereby tyrosine phosphorylation of the erythrocyte anion transporter, band 3, triggers membrane destabilization, vesiculation, and fragmentation, we discovered a SH2 signature motif positioned between membrane-spanning helices 4 and 5. Evidence that this exposed cytoplasmic sequence contributes to a functional SH2-like domain is provided by observations that: (i) it contains the most conserved sequence of SH2 domains, GSFLVR; (ii) it binds the tyrosine phosphorylated cytoplasmic domain of band 3 (cdb3-PO4) with Kd = 14 nM; (iii) binding of cdb3-PO4 to erythrocyte membranes is inhibited both by antibodies against the SH2 signature sequence and dephosphorylation of cdb3-PO4; (iv) label transfer experiments demonstrate the covalent transfer of photoactivatable biotin from isolated cdb3-PO4 (but not cdb3) to band 3 in erythrocyte membranes; and (v) phosphorylation-induced binding of cdb3-PO4 to the membrane-spanning domain of band 3 in intact cells causes global changes in membrane properties, including (i) displacement of a glycolytic enzyme complex from the membrane, (ii) inhibition of anion transport, and (iii) rupture of the band 3-ankyrin bridge connecting the spectrin-based cytoskeleton to the membrane...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27836504/nuclear-mechanical-resilience-but-not-stiffness-is-modulated-by-%C3%AE-ii-spectrin
#7
Travis J Armiger, Stephen T Spagnol, Kris Noel Dahl
Spectrins are multi-domain, elastic proteins that provide elasticity to the plasma membrane of erythrocytes and select nucleated cells. Spectrins have also been found in the nucleus of non-erythrocytes, but their function remains to be uncovered. It has been hypothesized that a spring-like spectrin network exists within the lamina nucleoskeleton, however, experiments testing a spectrin network׳s mechanical impact on the nucleus are lacking. Here, we knock-down levels of nuclear αII-spectrin with the goal of disrupting this nucleoskeletal spectrin network...
October 27, 2016: Journal of Biomechanics
https://www.readbyqxmd.com/read/27831662/loss-of-the-tgf-%C3%AE-effector-%C3%AE-2sp-promotes-genomic-instability
#8
Jian Chen, Vivek Shukla, Patrizia Farci, Jaclyn Andricovich, Wilma Jogunoori, Lawrence N Kwong, Lior H Katz, Kirti Shetty, Asif Rashid, Xiaoping Su, Jon White, Lei Li, Alan Yaoqi Wang, Boris Blechacz, Gottumukkala S Raju, Marta Davila, Bao-Ngoc Nguyen, John R Stroehlein, Junjie Chen, Sang Soo Kim, Heather Levin, Keigo Machida, Hidekazu Tsukamoto, Peter Michaely, Alexandros Tzatsos, Lopa Mishra
Exposure to genotoxins such as ethanol-derived acetaldehyde leads to DNA damage and liver injury, and promotes the development of cancer. We report here a major role for the TGF-β/Smad3 adaptor β2-Spectrin (β2SP, gene Sptbn1) in maintaining genomic stability following alcohol-induced DNA damage. β2SP supports DNA repair through β2SP-dependent activation of Fancd2, a core component of the Fanconi anemia complex. Loss of β2SP leads to decreased Fancd2 levels and sensitizes β2SP mutants to DNA damage by ethanol treatment, leading to phenotypes that closely resemble those observed in animals lacking both Aldh2 and Fancd2, and resemble human fetal alcohol syndrome...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27792725/md-dpd-multiscale-framework-for-predicting-morphology-and-stresses-of-red-blood-cells-in-health-and-disease
#9
Hung-Yu Chang, Xuejin Li, He Li, George Em Karniadakis
Healthy red blood cells (RBCs) have remarkable deformability, squeezing through narrow capillaries as small as 3 microns in diameter without any damage. However, in many hematological disorders the spectrin network and lipid bilayer of diseased RBCs may be significantly altered, leading to impaired functionality including loss of deformability. We employ a two-component whole-cell multiscale model to quantify the biomechanical characteristics of the healthy and diseased RBCs, including Plasmodium falciparum-infected RBCs (Pf-RBCs) and defective RBCs in hereditary disorders, such as spherocytosis and elliptocytosis...
October 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27782104/homozygous-syne1-mutation-causes-congenital-onset-of-muscular-weakness-with-distal-arthrogryposis-a-genotype-phenotype-correlation
#10
Matthias Baumann, Elisabeth Steichen-Gersdorf, Birgit Krabichler, Britt-Sabina Petersen, Ulrike Weber, Wolfgang M Schmidt, Johannes Zschocke, Thomas Müller, Reginald E Bittner, Andreas R Janecke
The exceptionally large SYNE1 (spectrin repeat-containing nuclear envelope protein 1) gene encodes different nesprin-1 isoforms, which are differentially expressed in striated muscle and in cerebellar and cerebral neurons. Nesprin-1 isoforms can function in cytoskeletal, nuclear, and vesicle anchoring. SYNE1 variants have been associated with a spectrum of neurological and neuromuscular disease. Homozygosity mapping combined with exome sequencing identified a disease-causing nonsense mutation in the ultimate exon of full-length SYNE1 transcript in an 8-year-old boy with distal arthrogryposis and muscular hypotonia...
October 26, 2016: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/27771897/profiling-of-signaling-proteins-in-penumbra-after-focal-photothrombotic-infarct-in-the-rat-brain-cortex
#11
Svetlana Demyanenko, Anatoly Uzdensky
In ischemic stroke, cell damage propagates from infarct core to surrounding tissue. To reveal proteins involved in neurodegeneration and neuroprotection, we explored the protein profile in penumbra surrounding the photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after Bengal Rose administration. Using antibody microarrays, we studied changes in expression of 224 signaling proteins 1, 4, or 24 h after photothrombotic infarct compared with untreated contralateral cortex...
October 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27756835/new-insights-on-hereditary-erythrocyte-membrane-defects
#12
REVIEW
Immacolata Andolfo, Roberta Russo, Antonella Gambale, Achille Iolascon
After the first proposed model of the red blood cell membrane skeleton 36 years ago, several additional proteins have been discovered during the intervening years, and their relationship with the pathogenesis of the related disorders have been somewhat defined. The knowledge of erythrocyte membrane structure is important because it represents the model for spectrin-based membrane skeletons in all cells and because defects in its structure underlie multiple hemolytic anemias. This review summarizes the main features of erythrocyte membrane disorders, dividing them into structural and altered permeability defects, focusing particularly on the most recent advances...
November 2016: Haematologica
https://www.readbyqxmd.com/read/27750484/phenelzine-protects-brain-mitochondrial-function-in-vitro-and-in-vivo-following-traumatic-brain-injury-by-scavenging-the-reactive-carbonyls-4-hydroxynonenal-and-acrolein-leading-to-cortical-histological-neuroprotection
#13
John E Cebak, Indrapal N Singh, Rachel L Hill, Juan A Wang, Edward D Hall
Lipid peroxidation (LP) is a key contributor to the pathophysiology of traumatic brain injury (TBI). Traditional antioxidant therapies are intended to scavenge the free radicals responsible for either initiation or propagation of LP. A more recently explored approach involves scavenging the terminal LP breakdown products that are highly reactive and neurotoxic carbonyl compounds, 4-hydroxynonenal (4-HNE) and acrolein (ACR), to prevent their covalent modification and rendering of cellular proteins nonfunctional leading to loss of ionic homeostasis, mitochondrial failure, and subsequent neuronal death...
December 2, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/27733621/identification-of-novel-nesprin-1-binding-partners-and-cytoplasmic-matrin-3-in-processing-bodies
#14
Dipen Rajgor, Jonathan G Hanley, Catherine M Shanahan
Nesprins are highly conserved spectrin repeat-containing scaffold proteins predominantly known to function at the nuclear envelope (NE). However, nesprin isoforms are emerging with localizations and scaffolding functions at sites away from the NE, suggesting their functions are more diverse than originally thought. In this study, we combined nesprin-1 coimmunoprecipitations with mass spectrometry to identify novel nesprin-1 binding partners for isoforms that localize to subcellular compartments beyond the NE...
December 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27720798/blast-waves-from-detonated-military-explosive-reduce-glur1-and-synaptophysin-levels-in-hippocampal-slice-cultures
#15
Marquitta Smith, Thuvan Piehler, Richard Benjamin, Karen L Farizatto, Morgan C Pait, Michael F Almeida, Vladimir V Ghukasyan, Ben A Bahr
Explosives create shockwaves that cause blast-induced neurotrauma, one of the most common types of traumatic brain injury (TBI) linked to military service. Blast-induced TBIs are often associated with reduced cognitive and behavioral functions due to a variety of factors. To study the direct effects of military explosive blasts on brain tissue, we removed systemic factors by utilizing rat hippocampal slice cultures. The long-term slice cultures were briefly sealed air-tight in serum-free medium, lowered into a 37°C water-filled tank, and small 1...
October 5, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27698030/cytoskeletal-integrators-the-spectrin-superfamily
#16
Ronald K H Liem
This review discusses the spectrin superfamily of proteins that function to connect cytoskeletal elements to each other, the cell membrane, and the nucleus. The signature domain is the spectrin repeat, a 106-122-amino-acid segment comprising three α-helices. α-actinin is considered to be the ancestral protein and functions to cross-link actin filaments. It then evolved to generate spectrin and dystrophin that function to link the actin cytoskeleton to the cell membrane, as well as the spectraplakins and plakins that link cytoskeletal elements to each other and to junctional complexes...
October 3, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27697928/nanoscopic-compartmentalization-of-membrane-protein-motion-at-the-axon-initial-segment
#17
David Albrecht, Christian M Winterflood, Mohsen Sadeghi, Thomas Tschager, Frank Noé, Helge Ewers
The axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and transmembrane molecules. During AIS establishment, a membrane diffusion barrier is formed between the axonal and somatodendritic domains. Recently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like structures has been discovered. However, whether this structure is related to the diffusion barrier function is unclear. Here, we performed single-particle tracking time-course experiments on hippocampal neurons during AIS development...
October 10, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27695656/leveraging-the-withered-tail-tip-phenotype-in-c-elegans-to-identify-proteins-that-influence-membrane-properties
#18
Emma Svensk, Jana Biermann, Sofia Hammarsten, Fredrik Magnusson, Marc Pilon
The properties of cellular membranes are critical for most cellular functions and are influenced by several parameters including phospholipid composition, integral and peripheral membrane proteins, and environmental conditions such as temperature. We previously showed that the C. elegans paqr-2 and iglr-2 mutants have a defect in membrane homeostasis and exhibit several distinct phenotypes, including a characteristic tail tip defect and cold intolerance. In the present study we report that screening for novel mutants with these 2 defects can lead to the identification of genes that are important contributors to membrane properties...
2016: Worm
https://www.readbyqxmd.com/read/27693510/characterization-of-novel-dystonia-musculorum-mutant-mice-implications-for-central-nervous-system-abnormality
#19
Masao Horie, Kazuyuki Mekada, Hiromi Sano, Yoshiaki Kikkawa, Satomi Chiken, Takuro Someya, Keisuke Saito, M Ibrahim Hossain, Masaaki Nameta, Kuniya Abe, Kenji Sakimura, Katsuhiko Ono, Atsushi Nambu, Atsushi Yoshiki, Hirohide Takebayashi
We identified a novel spontaneous mutant mouse showing motor symptoms that are similar to those of the dystonia musculorum (dt) mouse. The observations suggested that the mutant mice inherited the mild dt phenotype as an autosomal recessive trait. Linkage analysis showed that the causative gene was located near D1Mit373 and D1Mit410 microsatellite markers on chromosome 1, which are close to the dystonin (Dst) gene locus. To investigate whether Dst is the causative gene of the novel mutant phenotype, we crossed the mutant with Dst gene trap (Dst(Gt)) mice...
September 28, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27676701/trypsin-and-maldi-matrix-pre-coated-targets-simplify-sample-preparation-for-mapping-proteomic-distributions-within-biological-tissues-by-imaging-mass-spectrometry
#20
Faizan Zubair, Paul E Laibinis, William G Swisher, Junhai Yang, Jeffrey M Spraggins, Jeremy L Norris, Richard M Caprioli
Prefabricated surfaces containing alpha-cyano-4-hydroxycinnamic acid (CHCA) and trypsin have been developed to facilitate enzymatic digestion of endogenous tissue proteins prior to MALDI imaging mass spectrometry (IMS). Tissue sections are placed onto slides that were previously coated with CHCA and trypsin. After incubation to promote enzymatic digestion, the tissue is analyzed by MALDI IMS to determine the spatial distribution of the tryptic fragments. The peptides detected in the MALDI IMS dataset were identified by LC-MS/MS...
September 27, 2016: Journal of Mass Spectrometry: JMS
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