keyword
MENU ▼
Read by QxMD icon Read
search

Munc18

keyword
https://www.readbyqxmd.com/read/27911771/stability-folding-dynamics-and-long-range-conformational-transition-of-the-synaptic-t-snare-complex
#1
Xinming Zhang, Aleksander A Rebane, Lu Ma, Feng Li, Junyi Jiao, Hong Qu, Frederic Pincet, James E Rothman, Yongli Zhang
Synaptic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) couple their stepwise folding to fusion of synaptic vesicles with plasma membranes. In this process, three SNAREs assemble into a stable four-helix bundle. Arguably, the first and rate-limiting step of SNARE assembly is the formation of an activated binary target (t)-SNARE complex on the target plasma membrane, which then zippers with the vesicle (v)-SNARE on the vesicle to drive membrane fusion. However, the t-SNARE complex readily misfolds, and its structure, stability, and dynamics are elusive...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27896523/a-cd57-ctl-degranulation-assay-effectively-identifies-familial-hemophagocytic-lymphohistiocytosis-type-3-patients
#2
Masayuki Hori, Takahiro Yasumi, Saeko Shimodera, Hirofumi Shibata, Eitaro Hiejima, Hirotsugu Oda, Kazushi Izawa, Tomoki Kawai, Masataka Ishimura, Naoko Nakano, Ryutaro Shirakawa, Ryuta Nishikomori, Hidetoshi Takada, Satoshi Morita, Hisanori Horiuchi, Osamu Ohara, Eiichi Ishii, Toshio Heike
PURPOSE: Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is a genetic disorder that results in immune dysregulation. It requires prompt and accurate diagnosis. A natural killer (NK) cell degranulation assay is often used to screen for FHL3 patients. However, we recently encountered two cases of late-onset FHL3 carrying novel UNC13D missense mutations: in these cases, the degranulation assays using freshly isolated and interleukin (IL)-2-activated NK cells yielded contradictory results...
November 28, 2016: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27698125/mint3-potentiates-tlr3-4-and-rig-i-induced-ifn-%C3%AE-expression-and-antiviral-immune-responses
#3
Wanwan Huai, Hui Song, Zhongxia Yu, Wenwen Wang, Lihui Han, Takeharu Sakamoto, Motoharu Seiki, Lining Zhang, Qunye Zhang, Wei Zhao
Type I IFNs (IFN-α/β) play crucial roles in the elimination of invading viruses. Multiple immune cells including macrophages recognize viral infection through a variety of pattern recognition receptors, such as Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors, and initiate type I IFN secretion and subsequent antiviral immune responses. However, the mechanisms by which host immune cells can produce adequate amounts of type I IFNs and then eliminate viruses effectively remain to be further elucidated...
October 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27646276/the-munc18-1-domain-3a-hinge-loop-controls-syntaxin-1a-nanodomain-assembly-and-engagement-with-the-snare-complex-during-secretory-vesicle-priming
#4
Ravikiran Kasula, Ye Jin Chai, Adekunle T Bademosi, Callista B Harper, Rachel S Gormal, Isabel C Morrow, Eric Hosy, Brett M Collins, Daniel Choquet, Andreas Papadopulos, Frédéric A Meunier
Munc18-1 and syntaxin-1A control SNARE-dependent neuroexocytosis and are organized in nanodomains on the plasma membrane of neurons and neurosecretory cells. Deciphering the intra- and intermolecular steps via which they prepare secretory vesicles (SVs) for fusion is key to understanding neuronal and hormonal communication. Here, we demonstrate that expression of a priming-deficient mutant lacking 17 residues of the domain 3a hinge-loop (Munc18-1(Δ317-333)) in PC12 cells engineered to knockdown Munc18-1/2 markedly prolonged SV docking...
September 26, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27605709/regulation-of-ca2-channels-by-snap-25-via-recruitment-of-syntaxin-1-from-plasma-membrane-clusters
#5
Trine Lisberg Toft-Bertelsen, Iwona Ziomkiewicz, Sébastien Houy, Paulo S Pinheiro, Jakob B Sørensen
SNAP-25 regulates Ca(2+)-channels, with potentially important consequences for diseases involving an aberrant SNAP-25 expression level. How this regulation is executed mechanistically remains unknown. We have investigated this question in mouse adrenal chromaffin cells. We find that SNAP-25 inhibits Ca(2+)-currents, with the B-isoform being more potent than the A-isoform, but not when syntaxin-1 is cleaved by Botulinum Neurotoxin C. In contrast, syntaxin-1 inhibits Ca(2+)-currents independently of SNAP-25. Further experiments using immunostaining showed that endogenous or exogenous SNAP-25 expression recruits syntaxin-1 from clusters on the plasma membrane, thereby increasing the immunoavailability of syntaxin-1 and leading indirectly to Ca(2+)-current inhibition...
September 7, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27597757/beyond-the-snare-munc18-1-chaperones-%C3%AE-synuclein
#6
Mugdha Deshpande, Avital A Rodal
Early infantile epileptic encephalopathy (EIEE)-associated mutations in MUNC18-1 cause Munc18-1 misfolding and cellular aggregation. In this issue, Chai et al. (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201512016) find that Munc18-1 is a molecular chaperone for α-synuclein and that aggregated Munc18-1 EIEE-causing mutants promote α-synuclein aggregation.
September 12, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27597756/munc18-1-is-a-molecular-chaperone-for-%C3%AE-synuclein-controlling-its-self-replicating-aggregation
#7
Ye Jin Chai, Emma Sierecki, Vanesa M Tomatis, Rachel S Gormal, Nichole Giles, Isabel C Morrow, Di Xia, Jürgen Götz, Robert G Parton, Brett M Collins, Yann Gambin, Frédéric A Meunier
Munc18-1 is a key component of the exocytic machinery that controls neurotransmitter release. Munc18-1 heterozygous mutations cause developmental defects and epileptic phenotypes, including infantile epileptic encephalopathy (EIEE), suggestive of a gain of pathological function. Here, we used single-molecule analysis, gene-edited cells, and neurons to demonstrate that Munc18-1 EIEE-causing mutants form large polymers that coaggregate wild-type Munc18-1 in vitro and in cells. Surprisingly, Munc18-1 EIEE mutants also form Lewy body-like structures that contain α-synuclein (α-Syn)...
September 12, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27486879/consumption-of-pomegranates-improves-synaptic-function-in-a-transgenic-mice-model-of-alzheimer-s-disease
#8
Nady Braidy, Musthafa Mohamed Essa, Anne Poljak, Selvaraju Subash, Samir Al-Adawi, Thamilarasan Manivasagm, Arokiasamy Justin Thenmozhi, Lezanne Ooi, Perminder Sachdev, Gilles Guillemin
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by extracellular plaques containing abnormal Amyloid Beta (Aβ) aggregates, intracellular neurofibrillary tangles containing hyperphosphorylated tau protein, microglia-dominated neuroinflammation, and impairments in synaptic plasticity underlying cognitive deficits. Therapeutic strategies for the treatment of AD are currently limited. In this study, we investigated the effects of dietary supplementation of 4% pomegranate extract to a standard chow diet on neuroinflammation, and synaptic plasticity in APPsw/Tg2576 mice brain...
July 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27466336/distinct-functions-of-syntaxin-1-in-neuronal-maintenance-synaptic-vesicle-docking-and-fusion-in-mouse-neurons
#9
Gülçin Vardar, Shuwen Chang, Marife Arancillo, Yuan-Ju Wu, Thorsten Trimbuch, Christian Rosenmund
UNLABELLED: Neurotransmitter release requires the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes by SNARE proteins syntaxin-1 (Stx1), synaptosomal-associated protein 25 (SNAP-25), and synaptobrevin-2 (Syb2). In mammalian systems, loss of SNAP-25 or Syb2 severely impairs neurotransmitter release; however, complete loss of function studies for Stx1 have been elusive due to the functional redundancy between Stx1 isoforms Stx1A and Stx1B and the embryonic lethality of Stx1A/1B double knock-out (DKO) mice...
July 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27387979/frap-to-characterize-molecular-diffusion-and-interaction-in-various-membrane-environments
#10
Frédéric Pincet, Vladimir Adrien, Rong Yang, Jérôme Delacotte, James E Rothman, Wladimir Urbach, David Tareste
Fluorescence recovery after photobleaching (FRAP) is a standard method used to study the dynamics of lipids and proteins in artificial and cellular membrane systems. The advent of confocal microscopy two decades ago has made quantitative FRAP easily available to most laboratories. Usually, a single bleaching pattern/area is used and the corresponding recovery time is assumed to directly provide a diffusion coefficient, although this is only true in the case of unrestricted Brownian motion. Here, we propose some general guidelines to perform FRAP experiments under a confocal microscope with different bleaching patterns and area, allowing the experimentalist to establish whether the molecules undergo Brownian motion (free diffusion) or whether they have restricted or directed movements...
2016: PloS One
https://www.readbyqxmd.com/read/27358447/extension-of-helix-12-in-munc18-1-induces-vesicle-priming
#11
Anders S Munch, Girish H Kedar, Jan R T van Weering, Sonia Vazquez-Sanchez, Enqi He, Timon André, Thimo Braun, Thomas H Söllner, Matthijs Verhage, Jakob B Sørensen
UNLABELLED: Munc18-1 is essential for vesicle fusion and participates in the docking of large dense-core vesicles to the plasma membrane. Recent structural data suggest that conformational changes in the 12th helix of the Munc18-1 domain 3a within the Munc18-1:syntaxin complex result in an additional interaction with synaptobrevin-2/VAMP2 (vesicle-associated membrane protein 2), leading to SNARE complex formation. To test this hypothesis in living cells, we examined secretion from Munc18-1-null mouse adrenal chromaffin cells expressing Munc18-1 mutants designed to either perturb the extension of helix 12 (Δ324-339), block its interaction with synaptobrevin-2 (L348R), or extend the helix to promote coil-coil interactions with other proteins (P335A)...
June 29, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27268412/expression-and-localization-of-x11-family-proteins-in-neurons
#12
Rika Motodate, Yuhki Saito, Saori Hata, Toshiharu Suzuki
The X11/Mint family of proteins comprises X11/X11α/Mint1, X11L/X11β/Mint2, and X11L2/X11γ/Mint3. Each of these molecules is an adaptor protein that contains a phosphotyrosine interaction/binding (PI/PTB) and two PDZ domains in its carboxy-terminal region. X11/Mint family members associate with a broad spectrum of membrane proteins, including Alzheimer's β-amyloid precursor protein (APP), alcadeins, and low density lipoprotein receptor proteins, as well as various cytoplasmic proteins including Arf, kalirin-7, and Munc18...
September 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27243006/the-secret-life-of-tethers-the-role-of-tethering-factors-in-snare-complex-regulation
#13
REVIEW
Michelle L Dubuke, Mary Munson
Trafficking in eukaryotic cells is a tightly regulated process to ensure correct cargo delivery to the proper destination organelle or plasma membrane. In this review, we focus on how the vesicle fusion machinery, the SNARE complex, is regulated by the interplay of the multisubunit tethering complexes (MTC) with the SNAREs and Sec1/Munc18 (SM) proteins. Although these factors are used in different stages of membrane trafficking, e.g., Golgi to plasma membrane transport vs. vacuolar fusion, and in a variety of diverse eukaryotic cell types, many commonalities between their functions are being revealed...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27213521/functional-synergy-between-the-munc13-c-terminal-c1-and-c2-domains
#14
Xiaoxia Liu, Alpay Burak Seven, Marcial Camacho, Victoria Esser, Junjie Xu, Thorsten Trimbuch, Bradley Quade, Lijing Su, Cong Ma, Christian Rosenmund, Josep Rizo
Neurotransmitter release requires SNARE complexes to bring membranes together, NSF-SNAPs to recycle the SNAREs, Munc18-1 and Munc13s to orchestrate SNARE complex assembly, and Synaptotagmin-1 to trigger fast Ca(2+)-dependent membrane fusion. However, it is unclear whether Munc13s function upstream and/or downstream of SNARE complex assembly, and how the actions of their multiple domains are integrated. Reconstitution, liposome-clustering and electrophysiological experiments now reveal a functional synergy between the C1, C2B and C2C domains of Munc13-1, indicating that these domains help bridging the vesicle and plasma membranes to facilitate stimulation of SNARE complex assembly by the Munc13-1 MUN domain...
2016: ELife
https://www.readbyqxmd.com/read/27184330/epilepsy-is-not-a-mandatory-feature-of-stxbp1-associated-ataxia-tremor-retardation-syndrome
#15
Janina Gburek-Augustat, Stefanie Beck-Woedl, Andreas Tzschach, Peter Bauer, Martin Schoening, Angelika Riess
BACKGROUND: Mutations in the STXBP1 gene (MUNC18-1) were first described to cause Ohtahara syndrome (Early infantile epileptic encephalopathy, EIEE)(12-14) characterized by very early infantile epileptic encephalopathy with frequent tonic spasms and a suppression-burst pattern on electroencephalogram. In the following years a wider phenotype was recognized having milder forms of epilepsies. All patients showed also intellectual disability and movement disorders. METHODS: Here, we present three female patients with an ataxia-tremor-retardation syndrome caused by a de novo STXBP1 mutation...
December 0: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/27141410/the-conditional-ko-approach-cre-lox-technology-in-human-neurons
#16
Christopher Patzke, Thomas C Südhof
The use of human pluripotent stem cells to model human diseases has become a new standard in biomedical sciences. To this end, patient-derived somatic cells are studied in vitro to mimic human pathological conditions. Here, we describe an alternative experimental strategy, the 'conditional KO approach', which allows engineering disease-relevant mutations in pluripotent stem cells from healthy donors. In combination with the Cre/Lox technology, this strategy enables us to study the molecular causes of human diseases independent of the genetic background or of genetic alterations induced by clonal selection...
2016: Rare Diseases
https://www.readbyqxmd.com/read/27103520/role-of-dha-in-aging-related-changes-in-mouse-brain-synaptic-plasma-membrane-proteome
#17
Vishaldeep K Sidhu, Bill X Huang, Abhishek Desai, Karl Kevala, Hee-Yong Kim
Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry-based protein quantitation combined with western blot or messenger RNA analysis...
May 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27091977/phosphorylation-of-synaptotagmin-1-controls-a-post-priming-step-in-pkc-dependent-presynaptic-plasticity
#18
Arthur P H de Jong, Marieke Meijer, Ingrid Saarloos, Lennart Niels Cornelisse, Ruud F G Toonen, Jakob B Sørensen, Matthijs Verhage
Presynaptic activation of the diacylglycerol (DAG)/protein kinase C (PKC) pathway is a central event in short-term synaptic plasticity. Two substrates, Munc13-1 and Munc18-1, are essential for DAG-induced potentiation of vesicle priming, but the role of most presynaptic PKC substrates is not understood. Here, we show that a mutation in synaptotagmin-1 (Syt1(T112A)), which prevents its PKC-dependent phosphorylation, abolishes DAG-induced potentiation of synaptic transmission in hippocampal neurons. This mutant also reduces potentiation of spontaneous release, but only if alternative Ca(2+) sensors, Doc2A/B proteins, are absent...
May 3, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27056679/presynaptic-inhibition-upon-cb1-or-mglu2-3-receptor-activation-requires-erk-mapk-phosphorylation-of-munc18-1
#19
Sabine K Schmitz, Cillian King, Christian Kortleven, Vincent Huson, Tim Kroon, Josta T Kevenaar, Desiree Schut, Ingrid Saarloos, Joost P Hoetjes, Heidi de Wit, Oliver Stiedl, Sabine Spijker, Ka Wan Li, Huibert D Mansvelder, August B Smit, Lennart Niels Cornelisse, Matthijs Verhage, Ruud F Toonen
Presynaptic cannabinoid (CB1R) and metabotropic glutamate receptors (mGluR2/3) regulate synaptic strength by inhibiting secretion. Here, we reveal a presynaptic inhibitory pathway activated by extracellular signal-regulated kinase (ERK) that mediates CB1R- and mGluR2/3-induced secretion inhibition. This pathway is triggered by a variety of events, from foot shock-induced stress to intense neuronal activity, and induces phosphorylation of the presynaptic protein Munc18-1. Mimicking constitutive phosphorylation of Munc18-1 results in a drastic decrease in synaptic transmission...
June 1, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27032672/granuphilin-exclusively-mediates-functional-granule-docking-to-the-plasma-membrane
#20
Kouichi Mizuno, Takuji Fujita, Hiroshi Gomi, Tetsuro Izumi
In regulated exocytosis, it is generally assumed that vesicles must stably "dock" at the plasma membrane before they are primed to become fusion-competent. However, recent biophysical analyses in living cells that visualize fluorescent secretory granules have revealed that exocytic behaviors are not necessarily uniform: some granules beneath the plasma membrane are resistant to Ca(2+)-triggered release, while others are accelerated to fuse without a pause for stable docking. These findings suggest that stable docking is unnecessary, and can even be inhibitory or nonfunctional, for fusion...
2016: Scientific Reports
keyword
keyword
32962
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"