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Exocytosis

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https://www.readbyqxmd.com/read/29352103/dynamic-cycling-of-t-snare-acylation-regulates-platelet-exocytosis
#1
Jinchao Zhang, Yunjie Huang, Jing Chen, Haining Zhu, Sidney W Whiteheart
Platelets regulate vascular integrity by secreting a host of molecules that promote hemostasis and its sequelae. Given the importance of platelet exocytosis, it is critical to understand how it is controlled. The t-SNAREs, SNAP-23 and syntaxin-11, lack classical transmembrane domains (TMDs), yet both are associated with platelet membranes and redistributed into cholesterol-dependent, lipid rafts when platelets were activated. Using metabolic labeling and hydroxylamine/HCl (HA) treatment, we showed that both contain thioester-linked acyl groups...
January 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29351997/spatiotemporal-organization-of-exocytosis-emerges-during-neuronal-shape-change
#2
Fabio L Urbina, Shawn M Gomez, Stephanie L Gupton
Neurite elongation and branching in developing neurons requires plasmalemma expansion, hypothesized to occur primarily via exocytosis. We posited that exocytosis in developing neurons and nonneuronal cells would exhibit distinct spatiotemporal organization. We exploited total internal reflection fluorescence microscopy to image vesicle-associated membrane protein (VAMP)-pHluorin-mediated exocytosis in mouse embryonic cortical neurons and interphase melanoma cells, and developed computer-vision software and statistical tools to uncover spatiotemporal aspects of exocytosis...
January 19, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29342984/amaranthus-caudatus-stimulates-insulin-secretion-in-goto-kakizaki-rats-a-model-of-diabetes-mellitus-type-2
#3
Silvia Zambrana, Lena C E Lundqvist, Virginia Veliz, Sergiu-Bogdan Catrina, Eduardo Gonzales, Claes-Göran Östenson
Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic nutraceutical property of an AC hydroethanolic extract that contains mainly sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)), in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats...
January 15, 2018: Nutrients
https://www.readbyqxmd.com/read/29342276/a-predictive-quantitative-model-of-spiking-activity-and-stimulus-secretion-coupling-in-oxytocin-neurons
#4
Jorge Maícas-Royo, Gareth Leng, Duncan J MacGregor
Oxytocin neurons of the rat hypothalamus project to the posterior pituitary where they secrete their products into the bloodstream. The pattern and quantity of that release depends on the afferent inputs to the neurons, on their intrinsic membrane properties, and on non-linear interactions between spiking activity and exocytosis: a given number of spikes will trigger more secretion when they arrive close together. Here we present a quantitative computational model of oxytocin neurons that can replicate the results of a wide variety of published experiments...
January 12, 2018: Endocrinology
https://www.readbyqxmd.com/read/29340618/mitochondrial-toxicity
#5
Joel N Meyer, Jessica H Hartman, Danielle F Mello
Recent decades have seen a rapid increase in reported toxic effects of drugs and pollutants on mitochondria. Researchers have also documented many genetic differences leading to mitochondrial diseases, currently reported to affect ∼1 person in 4,300, creating a large number of potential gene-environment interactions in mitochondrial toxicity. We briefly review this history, and then highlight cutting-edge areas of mitochondrial research including the role of mitochondrial reactive oxygen species in signaling; increased understanding of fundamental biological processes involved in mitochondrial homeostasis (DNA maintenance and mutagenesis, mitochondrial stress response pathways, fusion and fission, autophagy and biogenesis, and exocytosis); systemic effects resulting from mitochondrial stresses in specific cell types; mitochondrial involvement in immune function; the growing evidence of long-term effects of mitochondrial toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test chemicals for mitochondrial toxicity...
January 11, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29340032/c3g-promotes-a-selective-release-of-angiogenic-factors-from-activated-mouse-platelets-to-regulate-angiogenesis-and-tumor-metastasis
#6
Víctor Martín-Granado, Sara Ortiz-Rivero, Rita Carmona, Sara Gutiérrez-Herrero, Mario Barrera, Laura San-Segundo, Celia Sequera, Pedro Perdiguero, Francisco Lozano, Francisco Martín-Herrero, José Ramón González-Porras, Ramón Muñoz-Chápuli, Almudena Porras, Carmen Guerrero
Previous observations indicated that C3G (RAPGEF1) promotes α-granule release, evidenced by the increase in P-selectin exposure on the platelet surface following its activation. The goal of the present study is to further characterize the potential function of C3G as a modulator of the platelet releasate and its implication in the regulation of angiogenesis. Proteomic analysis revealed a decreased secretion of anti-angiogenic factors from activated transgenic C3G and C3G∆Cat platelets. Accordingly, the secretome from both transgenic platelets had an overall pro-angiogenic effect as evidenced by an in vitro capillary-tube formation assay with HUVECs (human umbilical vein endothelial cells) and by two in vivo models of heterotopic tumor growth...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339438/quantifying-exosome-secretion-from-single-cells-reveals-a-modulatory-role-for-gpcr-signaling
#7
Frederik Johannes Verweij, Maarten P Bebelman, Connie R Jimenez, Juan J Garcia-Vallejo, Hans Janssen, Jacques Neefjes, Jaco C Knol, Richard de Goeij-de Haas, Sander R Piersma, S Rubina Baglio, Matthijs Verhage, Jaap M Middeldorp, Anoek Zomer, Jacco van Rheenen, Marc G Coppolino, Ilse Hurbain, Graça Raposo, Martine J Smit, Ruud F G Toonen, Guillaume van Niel, D Michiel Pegtel
Exosomes are small endosome-derived extracellular vesicles implicated in cell-cell communication and are secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology are based on isolation procedures after secretion, precluding direct and dynamic insight into the mechanics of exosome biogenesis and the regulation of their release. In this study, we propose real-time visualization of MVB-PM fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive optical reporters that detect MVB-PM fusion using live total internal reflection fluorescence and dynamic correlative light-electron microscopy...
January 16, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29337043/membrane-permeable-rab27a-is-a-regulator-of-the-acrosome-reaction-role-of-geranylgeranylation-and-guanine-nucleotides
#8
Matías A Bustos, Ornella Lucchesi, María C Ruete, Claudia N Tomes
The acrosome reaction is the regulated exocytosis of mammalian sperm's single secretory granule, essential for fertilization. It relies on small GTPases, the cAMP binding protein Epac, and the SNARE complex, among other components. Here, we describe a novel tool to investigate Rab27-related signaling pathways: a hybrid recombinant protein consisting of human Rab27A fused to TAT, a cell penetrating peptide. With this tool, we aimed to unravel the connection between Rab3, Rab27 and Rap1 in sperm exocytosis and to deepen our understanding about how isoprenylation and guanine nucleotides influence the behaviour of Rab27 in exocytosis...
January 11, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29336451/the-uptake-retention-and-clearance-of-drug-loaded-dendrimer-nanoparticles-in-astrocytes-electrophysiological-quantification
#9
Helena H Chowdhury, Susana R Cerqueira, Nuno Sousa, Joaquim M Oliveira, Rui L Reis, Robert Zorec
Nanoparticle-based drug delivery systems may impose risks to patients due to potential toxicity associated with a lack of clearance from cells or prolonged carrier-cell retention. This work evaluates vesicular cell uptake, retention and the possible transfer of endocytosed methylprednisolone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into secretory vesicles of rat cultured astrocytes. The cells were incubated with NPs and unitary vesicle fusions/fissions with the plasma membrane were monitored employing high-resolution membrane capacitance measurements...
January 16, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29335562/cryo-em-structure-of-the-exocyst-complex
#10
Kunrong Mei, Yan Li, Shaoxiao Wang, Guangcan Shao, Jia Wang, Yuehe Ding, Guangzuo Luo, Peng Yue, Jun-Jie Liu, Xinquan Wang, Meng-Qiu Dong, Hong-Wei Wang, Wei Guo
The exocyst is an evolutionarily conserved octameric protein complex that mediates the tethering of post-Golgi secretory vesicles to the plasma membrane during exocytosis and is implicated in many cellular processes such as cell polarization, cytokinesis, ciliogenesis and tumor invasion. Using cryo-EM and chemical cross-linking MS (CXMS), we solved the structure of the Saccharomyces cerevisiae exocyst complex at an average resolution of 4.4 Å. Our model revealed the architecture of the exocyst and led to the identification of the helical bundles that mediate the assembly of the complex at its core...
January 15, 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29328021/the-presynaptic-ribbon-maintains-vesicle-populations-at-the-hair-cell-afferent-fiber-synapse
#11
Lars Becker, Michael E Schnee, Mamiko Niwa, Willy Sun, Stephan Maxeiner, Sara Talaei, Bechara Kachar, Mark A Rutherford, Anthony J Ricci
The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon's contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; high stimulus level rescued exocytosis in KO...
January 12, 2018: ELife
https://www.readbyqxmd.com/read/29328020/the-synaptic-ribbon-is-critical-for-sound-encoding-at-high-rates-and-with-temporal-precision
#12
Philippe Jean, David Lopez de la Morena, Susann Michanski, Lina María Jaime Tobón, Rituparna Chakrabarti, Maria Magdalena Picher, Jakob Neef, SangYong Jung, Mehmet Gültas, Stephan Maxeiner, Andreas Neef, Carolin Wichmann, Nicola Strenzke, Chad Grabner, Tobias Moser
We studied the role of the synaptic ribbon for sound encoding at the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a lack of synaptic ribbons and an assembly of several small active zones (AZs) at each synaptic contact. Spontaneous and sound-evoked firing rates of SGNs and their compound action potential were reduced, indicating impaired transmission at ribbonless IHC-SGN synapses. The temporal precision of sound encoding was impaired and the recovery of SGN-firing from adaptation indicated slowed synaptic vesicle (SV) replenishment...
January 12, 2018: ELife
https://www.readbyqxmd.com/read/29327200/exocyst-complex-member-exoc5-is-required-for-survival-of-hair-cells-and-spiral-ganglion-neurons-and-maintenance-of-hearing
#13
Byeonghyeon Lee, Jeong-In Baek, Hyehyun Min, Seung-Hyun Bae, Kyeonghye Moon, Min-A Kim, Ye-Ri Kim, Ben Fogelgren, Joshua H Lipschutz, Kyu-Yup Lee, Jinwoong Bok, Un-Kyung Kim
The exocyst, an octameric protein complex consisting of Exoc1 through Exoc8, was first determined to regulate exocytosis by targeting vesicles to the plasma membrane in yeast to mice. In addition to this fundamental role, the exocyst complex has been implicated in other cellular processes. In this study, we investigated the role of the exocyst in cochlear development and hearing by targeting EXOC5, a central exocyst component. Deleting Exoc5 in the otic epithelium with widely used Cre lines resulted in early lethality...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29326040/downregulation-of-exocyst-sec10-accelerates-kidney-tubule-cell-recovery-through-enhanced-cell-migration
#14
Mi Ra Noh, Hee-Seong Jang, Dae-Kyu Song, Seong-Ryong Lee, Joshua H Lipschutz, Kwon Moo Park, Jee In Kim
Migration of surviving kidney tubule cells after sub-lethal injury, for example ischemia/reperfusion (I/R), plays a critical role in recovery. Exocytosis is known to be involved in cell migration, and a key component in exocytosis is the highly-conserved eight-protein exocyst complex. We investigated the expression of a central exocyst complex member, Sec10, in kidneys following I/R injury, as well as the role of Sec10 in wound healing following scratch injury of cultured Madin-Darby canine kidney (MDCK) cells...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29320738/trapping-of-syntaxin1a-in-presynaptic-nanoclusters-by-a-clinically-relevant-general-anesthetic
#15
Adekunle T Bademosi, James Steeves, Shanker Karunanithi, Oressia H Zalucki, Rachel S Gormal, Shu Liu, Elsa Lauwers, Patrik Verstreken, Victor Anggono, Frederic A Meunier, Bruno van Swinderen
Propofol is the most commonly used general anesthetic in humans. Our understanding of its mechanism of action has focused on its capacity to potentiate inhibitory systems in the brain. However, it is unknown whether other neural mechanisms are involved in general anesthesia. Here, we demonstrate that the synaptic release machinery is also a target. Using single-particle tracking photoactivation localization microscopy, we show that clinically relevant concentrations of propofol and etomidate restrict syntaxin1A mobility on the plasma membrane, whereas non-anesthetic analogs produce the opposite effect and increase syntaxin1A mobility...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29319803/down-regulation-of-glutamate-release-from-hippocampal-neurons-by-sialidase
#16
Minami Akira, Ami Ishii, Sumika Shimba, Takahiro Kano, Eri Fujioka, Saki Sai, Nagisa Oshio, Sayaka Ishibashi, Tadanobu Takahashi, Yuuki Kurebayashi, Hiroaki Kanazawa, Nobuhiro Yuki, Tadamune Otsubo, Kiyoshi Ikeda, Takashi Suzuki
Sialidase, which removes sialic acid residues in sialylglycoconjugates, is essential for hippocampal memory and synaptic plasticity. Enzyme activity of sialidase is rapidly increased in response to neural excitation. Because sialic acid bound to gangliosides such as the tetra-sialoganglioside GQ1b is crucial for calcium signaling and neurotransmitter release, neural activity-dependent removal of sialic acid may affect hippocampal neurotransmission. In the present study, we found that 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (DANA), a sialidase inhibitor, increased expression of ganglioside GQ1b/GT1a in hippocampal acute slices...
January 8, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/29319366/effects-of-subchronic-acrylamide-treatment-on-the-endocrine-pancreas-of-juvenile-male-wistar-rats
#17
M Stošić, M Matavulj, J Marković
Acrylamide (AA) is a well-known industrial monomer with carcinogenic, mutagenic, neurotoxic and endocrine disruptive effects on living organisms. AA has been the subject of renewed interest owing to its presence in various food products. We investigated the potential adverse effects of oral AA treatment on the endocrine pancreas of juvenile rats using histochemical, immunohistochemical, stereological and biochemical methods. Thirty juvenile male Wistar rats were divided into one control and two AA treatment groups: one treated with 25 mg/kg AA and the other treated with 50 mg/kg AA for 21 days...
January 10, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29317199/polarized-light-microscopy-reveals-physiological-and-drug-induced-changes-in-surfactant-membrane-assembly-in-alveolar-type-ii-pneumocytes
#18
Thomas Haller, Alejandro Cerrada, Kristian Pfaller, Peter Braubach, Edward Felder
In alveolar type II (AT II) cells, pulmonary surfactant (PS) is synthetized, stored and exocytosed from lamellar bodies (LBs), specialized large secretory organelles. By applying polarization microscopy (PM), we confirm a specific optical anisotropy of LBs, which indicates a liquid-crystalline mesophase of the stored surfactant phospholipids (PL) and an unusual case of a radiation-symmetric, spherocrystalline organelle. Evidence is shown that the degree of anisotropy is dependent on the amount of lipid layers and their degree of hydration, but unaffected by acutely modulating vital cell parameters like intravesicular pH or cellular energy supply...
January 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29312551/phosphorylation-of-rab37-by-protein-kinase-c-alpha-inhibits-the-exocytosis-function-and-metastasis-suppression-activity-of-rab37
#19
Hong-Tai Tzeng, Tsung-Hsin Li, Yen-An Tang, Chung-Han Tsai, Pei-Jung Frank Lu, Wu-Wei Lai, Chi-Wu Chiang, Yi-Ching Wang
We previously identified a novel Rab small GTPase protein, Rab37, which plays a critical role in regulating exocytosis of secreted glycoproteins, tissue inhibitor of metalloproteinases 1 (TIMP1) to suppress lung cancer metastasis. Patients with preserved Rab37 protein expression were associated with better prognosis. However, a significant number of the patients with preserved Rab37 expression showed poor survival. In addition, the molecular mechanism for the regulation of Rab37-mediated exocytosis remained to be further identified...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29306934/gliotransmitters-and-cytokines-in-the-control-of-blood-brain-barrier-permeability
#20
REVIEW
Elena D Osipova, Oxana V Semyachkina-Glushkovskaya, Andrey V Morgun, Natalia V Pisareva, Natalia A Malinovskaya, Elizaveta B Boitsova, Elena A Pozhilenkova, Olga A Belova, Vladimir V Salmin, Tatiana E Taranushenko, Mami Noda, Alla B Salmina
The contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions...
January 8, 2018: Reviews in the Neurosciences
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