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Exocytosis

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https://www.readbyqxmd.com/read/29163167/experimental-evaluation-of-the-transport-mechanisms-of-poifn-%C3%AE-in-caco-2-cells
#1
Xin Liu, Sidi Zheng, Yue Qin, Wenya Ding, Yabin Tu, Xingru Chen, Yunzhou Wu, Li Yanhua, Xuehui Cai
For the development of an efficient intestinal delivery system for Porcine interferon-α (PoIFN-α), the understanding of transport mechanisms of which in the intestinal cell is essential. In this study, we investigated the absorption mechanisms of PoIFN-α in intestine cells. Caco-2 cells and fluorescein isothiocyanate-labeled (FITC)-PoIFN-α were used to explore the whole transport process, including endocytosis, intracellular trafficking, exocytosis, and transcytosis. Via various techniques, the transport pathways of PoIFN-α in Caco-2 cells and the mechanisms were clarified...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29163046/rim-binding-protein-2-promotes-a-large-number-of-cav1-3-ca-2-channels-and-contributes-to-fast-synaptic-vesicle-replenishment-at-hair-cell-active-zones
#2
Stefanie Krinner, Tanvi Butola, SangYong Jung, Carolin Wichmann, Tobias Moser
Ribbon synapses of inner hair cells (IHCs) mediate high rates of synchronous exocytosis to indefatigably track the stimulating sound with sub-millisecond precision. The sophisticated molecular machinery of the inner hair cell active zone realizes this impressive performance by enabling a large number of synaptic voltage-gated CaV1.3 Ca(2+)-channels, their tight coupling to synaptic vesicles (SVs) and fast replenishment of fusion competent SVs. Here we studied the role of RIM-binding protein 2 (RIM-BP2)-a multidomain cytomatrix protein known to directly interact with Rab3 interacting molecules (RIMs), bassoon and CaV1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29162819/exocytosis-coordinated-mechanisms-for-tip-growth-underlie-pollen-tube-growth-guidance
#3
Nan Luo, An Yan, Gang Liu, Jingzhe Guo, Duoyan Rong, Masahiro M Kanaoka, Zhen Xiao, Guanshui Xu, Tetsuya Higashiyama, Xinping Cui, Zhenbiao Yang
Many tip-growing cells are capable of responding to guidance cues, during which cells precisely steer their growth toward the source of guidance signals. Though several players in signal perception have been identified, little is known about the downstream signaling that controls growth direction during guidance. Here, using combined modeling and experimental studies, we demonstrate that the growth guidance of Arabidopsis pollen tubes is regulated by the signaling network that controls tip growth. Tip-localized exocytosis plays a key role in this network by integrating guidance signals with the ROP1 Rho GTPase signaling and coordinating intracellular signaling with cell wall mechanics...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29161591/cell-invasion-in%C3%A2-vivo-via-rapid-exocytosis-of-a-transient-lysosome-derived-membrane-domain
#4
Kaleb M Naegeli, Eric Hastie, Aastha Garde, Zheng Wang, Daniel P Keeley, Kacy L Gordon, Ariel M Pani, Laura C Kelley, Meghan A Morrissey, Qiuyi Chi, Bob Goldstein, David R Sherwood
Invasive cells use small invadopodia to breach basement membrane (BM), a dense matrix that encases tissues. Following the breach, a large protrusion forms to clear a path for tissue entry by poorly understood mechanisms. Using RNAi screening for defects in Caenorhabditis elegans anchor cell (AC) invasion, we found that UNC-6(netrin)/UNC-40(DCC) signaling at the BM breach site directs exocytosis of lysosomes using the exocyst and SNARE SNAP-29 to form a large protrusion that invades vulval tissue. Live-cell imaging revealed that the protrusion is enriched in the matrix metalloprotease ZMP-1 and transiently expands AC volume by more than 20%, displacing surrounding BM and vulval epithelium...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29161585/localized-lysosome-exocytosis-helps-breach-tissue-barriers
#5
Shaohe Wang, Kenneth M Yamada
Cell invasion across basement membrane barriers is important in both normal development and cancer metastasis. In this issue of Developmental Cell, Naegeli et al. (2017) identify a mechanism for breaching basement membranes. Localized lysosome exocytosis fuels generation of large, invasive cellular protrusions that expand tiny basement membrane openings.
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29160768/diverse-modes-of-synaptic-signaling-regulation-and-plasticity-distinguish-classes-of-c-elegans-glutamatergic-neurons
#6
Donovan Ventimiglia, Cornelia I Bargmann
Synaptic vesicle release properties vary between neuronal cell types, but in most cases the molecular basis of this heterogeneity is unknown. Here, we compare in vivo synaptic properties of two neuronal classes in the C. elegans central nervous system, using VGLUT-pHluorin to monitor synaptic vesicle exocytosis and retrieval in intact animals. We show that the glutamatergic sensory neurons AWC(ON) and ASH have distinct synaptic dynamics associated with tonic and phasic synaptic properties, respectively. Exocytosis in ASH and AWC(ON) is differentially affected by SNARE-complex regulators that are present in both neurons: phasic ASH release is strongly dependent on UNC-13, whereas tonic AWC(ON) release relies upon UNC-18 and on the protein kinase C homolog PKC-1...
November 21, 2017: ELife
https://www.readbyqxmd.com/read/29150658/differential-regulation-of-synaptic-ap-2-clathrin-vesicle-uncoating-in-synaptic-plasticity
#7
Ermes Candiello, Ratnakar Mishra, Bernhard Schmidt, Olaf Jahn, Peter Schu
AP-1/σ1B-deficiency causes X-linked intellectual disability. AP-1/σ1B -/- mice have impaired synaptic vesicle recycling, fewer synaptic vesicles and enhanced endosome maturation mediated by AP-1/σ1A. Despite defects in synaptic vesicle recycling synapses contain two times more endocytic AP-2 clathrin-coated vesicles. We demonstrate increased formation of two classes of AP-2/clathrin coated vesicles. One which uncoats readily and a second with a stabilised clathrin coat. Coat stabilisation is mediated by three molecular mechanisms: reduced recruitment of Hsc70 and synaptojanin1 and enhanced μ2/AP-2 phosphorylation and activation...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29148696/the-epidermal-penetration-of-gold-nanoparticles-and-its-underlying-mechanism-based-on-human-reconstructed-3d-episkin-tm-model
#8
Fang Hao, Xiaoting Jin, Qian S Liu, Qunfang Zhou, Guibin Jiang
Nanomaterials are widely used in diverse aspects and their translocation behavior through the skin would be helpful in understanding the corresponding exposure risks. To reveal how surface functionalization of nanoparticles influence the skin penetration, three kinds of gold nanoparticles (GNPs) with negatively, neutrally and positively charged surfaces, i.e. cetyltrimethyl ammonium bromide-coated GNPs (CTAB@GNP), polyvinyl pyrrolidone-coated GNPs (PVP@GNP), and citrate-coated GNPs (Citrate@GNP), were studied using human reconstructed 3D EpiskinTM model...
November 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29141910/munc13-proteins-control-regulated-exocytosis-in-mast-cells
#9
Elsa M Rodarte, Marco A Ramos, Alfredo J Davalos, Daniel C Moreira, David S Moreno, Eduardo I Cardenas, Alejandro I Rodarte, Youlia Petrova, Sofia Molina, Luis E Rendon, Elizabeth Sanchez, Keegan Breaux, Alejandro Tortoriello, John Manllo, Erika A Gonzalez, Michael J Tuvim, Burton F Dickey, Alan R Burns, Ruth Heidelberger, Roberto Adachi
Mast cells (MCs) are involved in host defenses against pathogen and inflammation. Stimulated MCs release substances stored in their granules via regulated exocytosis. In other cell types, Munc13 (mammalian homolog of C. elegans uncoordinated gene 13) proteins play essential roles in regulated exocytosis. Here, we found that MCs express Munc13-2 and -4, and studied their roles using global and conditional knockout (KO) mice. In a model of systemic anaphylaxis, we found no difference between WT and Munc13-2 KO mice, but global and MC-specific Munc13-4 KO mice developed less hypothermia...
November 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29135027/acrosomal-alkalization-triggers-ca-2-release-and-acrosome-reaction-in-mammalian-spermatozoa
#10
EDITORIAL
Julio C Chávez, José L De la Vega-Beltrán, Omar José, Paulina Torres, Takuya Nishigaki, Claudia L Treviño, Alberto Darszon
The sperm acrosome reaction (AR), an essential event for mammalian fertilization, involves Ca(2+) permeability changes leading to exocytosis of the acrosomal vesicle. The acrosome, an intracellular Ca(2+) store whose luminal pH is acidic, contains hydrolytic enzymes. It is known that acrosomal pH (pHacr ) increases during capacitation and this correlates with spontaneous AR. Some AR inducers increase intracellular Ca(2+) concentration ([Ca(2+) ]i ) through Ca(2+) release from internal stores, mainly the acrosome...
November 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29133430/the-dual-function-of-the-polybasic-juxtamembrane-region-of-syntaxin-1a-in-clamping-spontaneous-release-and-stimulating-ca-2-triggered-release-in-neuroendocrine-cells
#11
Dafna Singer-Lahat, Noa Barak-Broner, Anton Sheinin, Dafna Greitzer-Antes, Izhak Michaelevski, Ilana Lotan
The exact function of the polybasic juxtamembrane region (5RK) of the plasma membrane neuronal SNARE, syntaxin 1A (Syx), in vesicle exocytosis, although widely studied, is currently not clear. Here, we addressed the role of 5RK in Ca(2+)-triggered release, using our Syx-based intramolecular FRET probe, which previously allowed us to resolve a depolarization-induced Ca(+2)- dependent close-to-open transition (CDO) of Syx that occurs concomitant with evoked release, both in PC12 cells and hippocampal neurons and was abolished upon charge neutralization of 5RK...
November 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29129207/fusion-pore-in-exocytosis-more-than-an-exit-gate-a-%C3%AE-cell-perspective
#12
REVIEW
Benoit Hastoy, Anne Clark, Patrik Rorsman, Jochen Lang
Secretory vesicle exocytosis is a fundamental biological event and the process by which hormones (like insulin) are released into the blood. Considerable progress has been made in understanding this precisely orchestrated sequence of events from secretory vesicle docked at the cell membrane, hemifusion, to the opening of a membrane fusion pore. The exact biophysical and physiological regulation of these events implies a close interaction between membrane proteins and lipids in a confined space and constrained geometry to ensure appropriate delivery of cargo...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29127297/rab5-is-critical-for-snap23-regulated-granule-granule-fusion-during-compound-exocytosis
#13
Ofir Klein, Amit Roded, Neta Zur, Nurit P Azouz, Olga Pasternak, Koret Hirschberg, Ilan Hammel, Paul A Roche, Ayaka Yatsu, Mitsunori Fukuda, Stephen J Galli, Ronit Sagi-Eisenberg
Compound exocytosis is considered the most massive mode of exocytosis, during which the membranes of secretory granules (SGs) fuse with each other to form a channel through which the entire contents of their granules is released. The underlying mechanisms of compound exocytosis remain largely unresolved. Here we show that the small GTPase Rab5, a known regulator of endocytosis, is pivotal for compound exocytosis in mast cells. Silencing of Rab5 shifts receptor-triggered secretion from a compound to a full exocytosis mode, in which SGs individually fuse with the plasma membrane...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29125546/hereditary-nephrogenic-diabetes-insipidus-pathophysiology-and-possible-treatment-an-update
#14
REVIEW
Serena Milano, Monica Carmosino, Andrea Gerbino, Maria Svelto, Giuseppe Procino
Under physiological conditions, excessive loss of water through the urine is prevented by the release of the antidiuretic hormone arginine-vasopressin (AVP) from the posterior pituitary. In the kidney, AVP elicits a number of cellular responses, which converge on increasing the osmotic reabsorption of water in the collecting duct. One of the key events triggered by the binding of AVP to its type-2 receptor (AVPR2) is the exocytosis of the water channel aquaporin 2 (AQP2) at the apical membrane the principal cells of the collecting duct...
November 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29123471/vglut2-trafficking-is-differentially-regulated-by-adaptor-proteins-ap-1-and-ap-3
#15
Haiyan Li, Magda S Santos, Chihyung K Park, Yuriy Dobry, Susan M Voglmaier
Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on glutamate loading into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern of expression in adult brain that broadly distinguishes cortical (VGLUT1) and subcortical (VGLUT2) systems, and correlates with distinct physiological properties in synapses expressing these isoforms. Differential trafficking of VGLUT1 and 2 has been suggested to underlie their functional diversity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29123470/regulation-of-ampa-receptor-trafficking-by-protein-ubiquitination
#16
REVIEW
Jocelyn Widagdo, Sumasri Guntupalli, Se E Jang, Victor Anggono
The molecular mechanisms underlying plastic changes in the strength and connectivity of excitatory synapses have been studied extensively for the past few decades and remain the most attractive cellular models of learning and memory. One of the major mechanisms that regulate synaptic plasticity is the dynamic adjustment of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor content on the neuronal plasma membrane. The expression of surface AMPA receptors (AMPARs) is controlled by the delicate balance between the biosynthesis, dendritic transport, exocytosis, endocytosis, recycling and degradation of the receptors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29123102/semisynthetic-fluorescent-ph-sensors-for-imaging-exocytosis-and-endocytosis
#17
Magalie Martineau, Agila Somasundaram, Jonathan B Grimm, Todd D Gruber, Daniel Choquet, Justin W Taraska, Luke D Lavis, David Perrais
The GFP-based superecliptic pHluorin (SEP) enables detection of exocytosis and endocytosis, but its performance has not been duplicated in red fluorescent protein scaffolds. Here we describe "semisynthetic" pH-sensitive protein conjugates with organic fluorophores, carbofluorescein, and Virginia Orange that match the properties of SEP. Conjugation to genetically encoded self-labeling tags or antibodies allows visualization of both exocytosis and endocytosis, constituting new bright sensors for these key steps of synaptic transmission...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29122960/mir-335-overexpression-impairs-insulin-secretion-through-defective-priming-of-insulin-vesicles
#18
Vishal A Salunkhe, Jones K Ofori, Nikhil R Gandasi, Sofia A Salö, Sofia Hansson, Markus E Andersson, Anna Wendt, Sebastian Barg, Jonathan L S Esguerra, Lena Eliasson
MicroRNAs contribute to the maintenance of optimal cellular functions by fine-tuning protein expression levels. In the pancreatic β-cells, imbalances in the exocytotic machinery components lead to impaired insulin secretion and type 2 diabetes (T2D). We hypothesize that dysregulated miRNA expression exacerbates β-cell dysfunction, and have earlier shown that islets from the diabetic GK-rat model have increased expression of miRNAs, including miR-335-5p (miR-335). Here, we aim to determine the specific role of miR-335 during development of T2D, and the influence of this miRNA on glucose-stimulated insulin secretion and Ca(2+)-dependent exocytosis...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29120672/an-electrostatic-and-probabilistic-simulation-model-to-describe-neurosecretion-at-the-synaptic-scale
#19
A E Macias-Medri, Jacinto A Liendo, Ricardo J Silva
A hybrid simulation model (macro-molecular dynamics and Monte Carlo method) is proposed to reproduce neurosecretion and exocytosis. A theory has been developed for vesicular dynamics based on quasi-static electric interactions and a simple transition-state model for the vesicular fusion. Under the non-equilibrium electric conditions in an electrolytic fluid, it is considered that the motion of each synaptic vesicle is influenced by electrostatic forces exerted by the membranes of the synaptic bouton, other vesicles, the intracellular and intravesicular fluids, and external elements to the neuron...
November 9, 2017: Network: Computation in Neural Systems
https://www.readbyqxmd.com/read/29118420/aav-mediated-transcription-factor-eb-tfeb-gene-delivery-ameliorates-muscle-pathology-and-function-in-the-murine-model-of-pompe-disease
#20
Francesca Gatto, Barbara Rossi, Antonietta Tarallo, Elena Polishchuk, Roman Polishchuk, Alessandra Carrella, Edoardo Nusco, Filomena Grazia Alvino, Francesca Iacobellis, Elvira De Leonibus, Alberto Auricchio, Graciana Diez-Roux, Andrea Ballabio, Giancarlo Parenti
Pompe disease (PD) is a metabolic myopathy due to acid alpha-glucosidase deficiency and characterized by extensive glycogen storage and impaired autophagy. We previously showed that modulation of autophagy and lysosomal exocytosis by overexpression of the transcription factor EB (TFEB) gene was effective in improving muscle pathology in PD mice injected intramuscularly with an AAV-TFEB vector. Here we have evaluated the effects of TFEB systemic delivery on muscle pathology and on functional performance, a primary measure of efficacy in a disorder like PD...
November 8, 2017: Scientific Reports
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