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Synaptotagmin

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https://www.readbyqxmd.com/read/29771357/a-promotive-effect-for-halofuginone-on-membrane-repair-and-synaptotagmin-7-levels-in-muscle-cells-of-dysferlin-null-mice
#1
Hila Barzilai-Tutsch, Melissa Dewulf, Christophe Lamaze, Gillian Butler Browne, Mark Pines, Orna Halevy
In the absence of dysferlin, skeletal muscle cells fail to reseal properly after injury, resulting in slow progress of the dysferlinopathy muscular dystrophy. Halofuginone, a leading agent in preventing fibrosis in muscular dystrophies, was tested for its effects on membrane resealing post-injury. A hypo-osmotic shock assay on myotubes derived from wild-type and dysferlin-null (dysf-/-) mice revealed that pre-treatment with halofuginone reduces the percentage of membrane-ruptured myotubes only in dysf-/- myotubes...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29769266/regulation-of-bdnf-release-by-arms-kidins220-through-modulation-of-synaptotagmin-iv-levels
#2
Saray López-Benito, Julia Sánchez-Sánchez, Verónica Brito, Laura Calvo, Silvia Lisa, María Torres-Valle, Mary E Palko, Cristina Vicente-García, Seila Fernández-Fernández, Juan P Bolaños, Silvia Ginés, Lino Tessarollo, Juan C Arévalo
BDNF is a growth factor with important roles in the nervous system in both physiological and pathological conditions, but the mechanisms controlling its secretion are not completely understood. Here, we show that ARMS/Kidins220 negatively regulates BDNF secretion in neurons from the central and peripheral nervous systems. Downregulation of the ARMS/Kidins220 protein in the adult mouse brain increases regulated BDNF secretion leading to its accumulation in the striatum. Interestingly, two mouse models of Huntington's disease (HD) showed increased levels of ARMS/Kidins220 in the hippocampus and regulated BDNF secretion deficits...
May 16, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29760174/snt-1-functions-as-the-ca-2-sensor-for-tonic-and-evoked-neurotransmitter-release-in-c-elegans
#3
Lei Li, Haowen Liu, Wei Wang, Mintu Chandra, Brett M Collins, Zhitao Hu
Synaptotagmin-1 (Syt1) binds Ca2+ through its tandem C2 domains (C2A and C2B) and triggers Ca2+ -dependent neurotransmitter release. Here we show that snt-1 , the homolog of mammalian Syt1, functions as the Ca2+ sensor for both tonic and evoked neurotransmitter release at the C. elegans neuromuscular junction. Mutations that disrupt Ca2+ binding in double C2 domains of SNT-1 significantly impaired tonic release, whereas disrupting Ca2+ binding in a single C2 domain had no effect, indicating that the Ca2+ binding of the two C2 domains is functionally redundant for tonic release...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29752624/g%C3%AE-%C3%AE-snare-interactions-and-their-behavioral-effects
#4
Simon Alford, Heidi Hamm, Shelagh Rodriguez, Zack Zurawski
Presynaptic terminals possess interlocking molecular mechanisms that control exocytosis. An example of such complexity is the modulation of release by presynaptic G Protein Coupled Receptors (GPCRs). GPCR ubiquity at synapses-GPCRs are present at every studied presynaptic terminal-underlies their critical importance in synaptic function. GPCRs mediate presynaptic modulation by mechanisms including via classical Gα effectors, but membrane-delimited actions of Gβγ can also alter probability of release by altering presynaptic ionic conductances...
May 11, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29741294/synaptotagmin-xiii-expression-and-peritoneal-metastasis-in-gastric-cancer
#5
M Kanda, D Shimizu, H Tanaka, C Tanaka, D Kobayashi, M Hayashi, H Takami, Y Niwa, S Yamada, T Fujii, H Sugimoto, Y Kodera
BACKGROUND: Peritoneal metastasis is a frequent cause of death in patients with gastric cancer. The aim of this study was to identify molecules responsible for mediating peritoneal metastasis of gastric cancer. METHODS: Transcriptome and bioinformatics analyses were conducted to identify molecules associated with peritoneal metastasis. The therapeutic effects of intraperitoneally administered small interfering (si) RNA were evaluated using mouse xenograft models...
May 9, 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29738707/synaptotagmins-tweak-functional-%C3%AE-cell-maturation
#6
Jennifer M Gilbert, Barak Blum
Immature β cells secrete insulin at a lower glucose threshold compared to mature β cells. In this issue of Developmental Cell, Huang et al. (2018) show that the increase in glucose threshold during β cell maturation is achieved through balance between the Ca2+ -sensitive synaptotagmin 7 and the Ca2+ -insensitive synaptotagmin 4.
May 7, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29718991/a-lipid-binding-loop-of-botulinum-neurotoxin-serotypes-b-dc-and-g-is-an-essential-feature-to-confer-their-exquisite-potency
#7
Daniel Stern, Jasmin Weisemann, Alexander Le Blanc, Laura von Berg, Stefan Mahrhold, Janett Piesker, Michael Laue, Peter B Luppa, Martin Bernhard Dorner, Brigitte Gertrud Dorner, Andreas Rummel
The exceptional toxicity of botulinum neurotoxins (BoNTs) is mediated by high avidity binding to complex polysialogangliosides and intraluminal segments of synaptic vesicle proteins embedded in the presynaptic membrane. One peculiarity is an exposed hydrophobic loop in the toxin's cell binding domain HC, which is located between the ganglioside and protein receptor-binding sites, and that is particularly pronounced in the serotypes BoNT/B, DC, and G sharing synaptotagmin as protein receptor. Here, we provide evidence that this HC loop is a critical component of their tripartite receptor recognition complex...
May 2, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29706534/ca-2-triggered-synaptic-vesicle-fusion-initiated-by-release-of-inhibition
#8
REVIEW
Axel T Brunger, Jeremy Leitz, Qiangjun Zhou, Ucheor B Choi, Ying Lai
Recent structural and functional studies of the synaptic vesicle fusion machinery suggest an inhibited tripartite complex consisting of neuronal soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs), synaptotagmin, and complexin prior to Ca2+ -triggered synaptic vesicle fusion. We speculate that Ca2+ -triggered fusion commences with the release of inhibition by Ca2+ binding to synaptotagmin C2 domains. Subsequently, fusion is assisted by SNARE complex zippering and by active membrane remodeling properties of synaptotagmin...
April 26, 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29672834/formation-of-g-wires-bimolecular-and-tetramolecular-quadruplex-cation-induced-structural-polymorphs-of-g-rich-dna-sequence-of-human-sytx-gene
#9
Saami Ahmed, Mahima Kaushik, Swati Chaudhary, Shrikant Kukreti
An exceptional property of auto-folding into a range of intra- as well as intermolecular quadruplexes by guanine-rich oligomers (GROs) of promoters, telomeres and various other genomic locations is still one of the most attractive areas of research at present times. The main reason for this attention is due to their established in vivo existence and biological relevance. Herein, the structural status of a 20-nt long G-rich sequence with two G5 stretches (SG20) is investigated using various biophysical and biochemical techniques...
April 19, 2018: Biopolymers
https://www.readbyqxmd.com/read/29670520/two-behavioral-tests-allow-a-better-correlation-between-cognitive-function-and-expression-of-synaptic-proteins
#10
Marta Balietti, Giorgia Fattorini, Arianna Pugliese, Daniele Marcotulli, Luca Bragina, Fiorenzo Conti
The molecular substrate of age-associated cognitive decline (AACD) is still elusive. Evidence indicates that AACD is related to synaptic impairment in hippocampus, but different hippocampal regions play different roles, with the dorsal hippocampus (DH) associated to spatial learning, and the ventral hippocampus (VH) crucial for emotionality. If changes in hippocampal function contributes to AACD, this contribution may be reflected in alterations of synaptic protein levels. A commonly used approach to investigate this issue is western blotting...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29656931/synaptotagmin-4-regulates-pancreatic-%C3%AE-cell-maturation-by-modulating-the-ca-2-sensitivity-of-insulin-secretion-vesicles
#11
Chen Huang, Emily M Walker, Prasanna K Dadi, Ruiying Hu, Yanwen Xu, Wenjian Zhang, Tiziana Sanavia, Jisoo Mun, Jennifer Liu, Gopika G Nair, Hwee Yim Angeline Tan, Sui Wang, Mark A Magnuson, Christian J Stoeckert, Matthias Hebrok, Maureen Gannon, Weiping Han, Roland Stein, David A Jacobson, Guoqiang Gu
Islet β cells from newborn mammals exhibit high basal insulin secretion and poor glucose-stimulated insulin secretion (GSIS). Here we show that β cells of newborns secrete more insulin than adults in response to similar intracellular Ca2+ concentrations, suggesting differences in the Ca2+ sensitivity of insulin secretion. Synaptotagmin 4 (Syt4), a non-Ca2+ binding paralog of the β cell Ca2+ sensor Syt7, increased by ∼8-fold during β cell maturation. Syt4 ablation increased basal insulin secretion and compromised GSIS...
April 12, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29625118/fus-causes-synaptic-hyperexcitability-in-drosophila-dendritic-arborization-neurons
#12
James B Machamer, Brian M Woolums, Gregory Fuller, Thomas E Lloyd
Mutations in the nuclear localization signal of the RNA binding protein FUS cause both Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). These mutations result in a loss of FUS from the nucleus and the formation of FUS-containing cytoplasmic aggregates in patients. To better understand the role of cytoplasmic FUS mislocalization in the pathogenesis of ALS, we identified a population of cholinergic neurons in Drosophila that recapitulate these pathologic hallmarks. Expression of mutant FUS or the Drosophila homolog, Cabeza (Caz), in class IV dendritic arborization neurons results in cytoplasmic mislocalization and axonal transport to presynaptic terminals...
April 3, 2018: Brain Research
https://www.readbyqxmd.com/read/29617377/inositol-1-4-5-trisphosphate-3-kinase-a-overexpressed-in-mouse-forebrain-modulates-synaptic-transmission-and-mglur-ltd-of-ca1-pyramidal-neurons
#13
Byungil Choi, Hyun Woo Lee, Seojung Mo, Jin Yong Kim, Hyun Wook Kim, Im Joo Rhyu, Eunhwa Hong, Yeon Kyung Lee, June-Seek Choi, Chong-Hyun Kim, Hyun Kim
Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) regulates the level of the inositol polyphosphates, inositol trisphosphate (IP3) and inositol tetrakisphosphate to modulate cellular signaling and intracellular calcium homeostasis in the central nervous system. IP3K-A binds to F-actin in an activity-dependent manner and accumulates in dendritic spines, where it is involved in the regulation of synaptic plasticity. IP3K-A knockout mice exhibit deficits in some forms of hippocampus-dependent learning and synaptic plasticity, such as long-term potentiation in the dentate gyrus synapses of the hippocampus...
2018: PloS One
https://www.readbyqxmd.com/read/29616096/a-comprehensive-analysis-of-the-predicted-targets-of-mir-642b-3p-associated-with-the-long-non-coding-rna-hoxa11-as-in-nsclc-cells
#14
Yu Zhang, Jie Luo, Xiao Wang, Han-Lin Wang, Xiu-Ling Zhang, Ting-Qing Gan, Gang Chen, Dian-Zhong Luo
Long non-coding RNA HOXA11 antisense RNA (HOXA11-AS) has been previously reported to be involved in the tumorigenesis and progression of ovarian cancer and glioma. However, the function of HOXA11-AS in lung cancer remains unclear. Following the knockdown of HOXA11-AS in A549 cells, a microarray analysis was performed in order to detect the differences in microRNA (miRNA/miR) profiles. Subsequently, miR-642b-3p was selected for further analysis. Four miRNA target prediction algorithms were used to identify potential target genes of miR-642b-3p...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29615494/small-molecules-that-inhibit-the-late-stage-of-munc13-4-dependent-secretory-granule-exocytosis-in-mast-cells
#15
Stephen Bruinsma, Declan J James, Melanie Quintana Serrano, Joseph Esquibel, Sang Su Woo, Elle Kielar-Grevstad, Ellen Crummy, Rehan Quraishi, Judy A Kowalchyk, Thomas F J Martin
Ca2+ -dependent secretory granule fusion with the plasma membrane is the final step for the exocytic release of inflammatory mediators, neuropeptides, and peptide hormones. Secretory cells use a similar protein machinery at late steps in the regulated secretory pathway employing protein isoforms from Rab, Sec1/Munc18, Munc13/CAPS, SNARE, and synaptotagmin protein families. However, no small molecule inhibitors of secretory granule exocytosis that target these proteins are currently available, but could have clinical utility...
April 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29593071/synaptotagmin-7-mediates-both-facilitation-and-asynchronous-release-at-granule-cell-synapses
#16
Josef Turecek, Wade G Regehr
When an action potential invades a presynaptic terminal it evokes large, brief Ca2+ signals that trigger vesicle fusion within milliseconds that is followed by a small residual Ca2+ (Cares ) signal. At many synapses Cares produces synaptic facilitation that lasts up to hundreds of milliseconds and, although less common, Cares can also evoke asynchronous release (AR) that persists for tens of milliseconds. The properties of facilitation and AR are very different, which suggests that they are mediated by distinct mechanisms...
March 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29578683/an-immunohistochemical-approach-to-understanding-the-organization-of-the-olfactory-system-in-the-cuttlefish-sepia-officinalis
#17
Alexia T Scaros, Roger Croll, Sebastien Baratte
Cephalopods are non-traditional but captivating models of invertebrate neurobiology, particularly in evolutionary comparisons. Cephalopod olfactory systems have striking similarities and fundamental differences with vertebrates, arthropods, and gastropods, raising questions about the ancestral origins of those systems. We describe here the organization and development of the olfactory system of the common cuttlefish, Sepia officinalis, using immunohistochemistry and in situ hybridization. FMRFamide and/or related peptides and histamine are putative neurotransmitters in olfactory sensory neurons...
March 26, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29573288/synaptotagmin-11-is-a-novel-hotspot-in-the-pathogenesis-of-parkin-linked-parkinson-s-disease-new-implications-for-clinical-targeting
#18
Hossein Sanjari Moghaddam, Mohammad Hadi Arabi
No abstract text is available yet for this article.
March 24, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29568072/regulation-of-synaptic-architecture-and-synaptic-vesicle-pools-by-nervous-wreck-at-drosophila-type-1b-glutamatergic-synapses
#19
Joon Haeng Hur, Sang-Hee Lee, A-Young Kim, Young Ho Koh
Nervous wreck (Nwk), a protein that is present at Type 1 glutamatergic synapses that contains an SH3 domain and an FCH motif, is a Drosophila homolog of the human srGAP3/MEGAP protein, which is associated with mental retardation. Confocal microscopy revealed that circles in Nwk reticulum enclosed T-shaped active zones (T-AZs) and partially colocalized with synaptic vesicle (SV) markers and both exocytosis and endocytosis components. Results from an electron microscopic (EM) analysis showed that Nwk proteins localized at synaptic edges and in SV pools...
March 23, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29519941/kinesin-1-is-a-new-actor-involved-in-platelet-secretion-and-thrombus-stability
#20
Frédéric Adam, Alexandre Kauskot, Mathieu Kurowska, Nicolas Goudin, Isabelle Munoz, Jean-Claude Bordet, Jian-Dong Huang, Marijke Bryckaert, Alain Fischer, Delphine Borgel, Geneviève de Saint Basile, Olivier D Christophe, Gaël Ménasché
OBJECTIVE: Platelet secretion is crucial for many physiological platelet responses. Even though several regulators of the fusion machinery for secretory granule exocytosis have been identified in platelets, the underlying mechanisms are not yet fully characterized. APPROACH AND RESULTS: By studying a mouse model (cKO [conditional knockout]Kif5b ) lacking Kif5b (kinesin-1 heavy chain) in its megakaryocytes and platelets, we evidenced unstable hemostasis characterized by an increase of blood loss associated to a marked tendency to rebleed in a tail-clip assay and thrombus instability in an in vivo thrombosis model...
May 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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