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https://www.readbyqxmd.com/read/28292915/a-cascade-of-multiple-proteins-and-lipids-catalyzes-membrane-fusion
#1
William Wickner, Josep Rizo
Recent studies suggest revisions to the SNARE paradigm of membrane fusion. Membrane tethers and/or SNAREs recruit proteins of the Sec 1/Munc18 family to catalyze SNARE assembly into trans-complexes. SNARE-domain zippering draws the bilayers into immediate apposition and provides a platform to position fusion triggers such as Sec 17/α-SNAP and/or synaptotagmin, which insert their apolar "wedge" domains into the bilayers, initiating the lipid rearrangements of fusion.
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28267240/integrated-functions-of-membrane-type-1-matrix-metalloproteinase-in-regulating-cancer-malignancy-beyond-a-proteinase
#2
REVIEW
Takeharu Sakamoto, Motoharu Seiki
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed in different types of invasive and proliferative cells, including cancer cells and stromal cells. MT1-MMP cleaves extracellular matrix proteins, membrane proteins, and other pericellular proteins, thereby changing the cellular microenvironment and regulating signal activation. Critical roles of protease activity in cancer cell proliferation, invasion, and metastasis have been demonstrated by many groups. MT1-MMP also has a non-protease activity in that it inhibits the oxygen-dependent suppression of hypoxia-inducible factors (HIFs) via Munc18-1-interacting protein 3 (Mint3) and thereby enhances the expression of HIF target genes...
March 7, 2017: Cancer Science
https://www.readbyqxmd.com/read/28265073/sm-protein-munc18-2-facilitates-transition-of-syntaxin-11-mediated-lipid-mixing-to-complete-fusion-for-t-lymphocyte-cytotoxicity
#3
Waldo A Spessott, Maria L Sanmillan, Margaret E McCormick, Vineet V Kulkarni, Claudio G Giraudo
The atypical lipid-anchored Syntaxin 11 (STX11) and its binding partner, the Sec/Munc (SM) protein Munc18-2, facilitate cytolytic granule release by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Patients carrying mutations in these genes develop familial hemophagocytic lymphohistiocytosis, a primary immunodeficiency characterized by impaired lytic granule exocytosis. However, whether a SNARE such as STX11, which lacks a transmembrane domain, can support membrane fusion in vivo is uncertain, as is the precise role of Munc18-2 during lytic granule exocytosis...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28137749/conformational-change-of-syntaxin-linker-region-induced-by-munc13s-initiates-snare-complex-formation-in-synaptic-exocytosis
#4
Shen Wang, Ucheor B Choi, Jihong Gong, Xiaoyu Yang, Yun Li, Austin L Wang, Xiaofei Yang, Axel T Brunger, Cong Ma
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin-1 adopts a closed conformation when bound to Munc18-1, preventing binding to synaptobrevin-2 and SNAP-25 to form the ternary SNARE complex. Although it is known that the MUN domain of Munc13-1 catalyzes the transition from the Munc18-1/syntaxin-1 complex to the SNARE complex, the molecular mechanism is unclear. Here, we identified two conserved residues (R151, I155) in the syntaxin-1 linker region as key sites for the MUN domain interaction...
March 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28118494/strain-dependent-effects-of-acute-alcohol-on-synaptic-vesicle-recycling-and-post-tetanic-potentiation-in-medial-glutamate-inputs-to-the-mouse-basolateral-amygdala
#5
Dominic A Gioia, Brian McCool
BACKGROUND: Inbred mouse strains are differentially sensitive to the acute effects of ethanol (EtOH) and are useful tools for examining how unique genomes differentially affect alcohol-related behaviors and physiology. DBA/2J mice have been shown to be sensitive to the acute anxiolytic effects of alcohol as well as the anxiogenic effects of withdrawal from chronic alcohol exposure, while B6 mice are resistant to both. Considering that the basolateral amygdala (BLA) is an important brain region for the acute and chronic effects of EtOH on fear and anxiety related behaviors, we hypothesized that there would be strain-dependent differences in the acute effects of EtOH in BLA slices...
January 24, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28116546/cortical-synaptic-transmission-and-plasticity-in-acute-liver-failure-are-decreased-by-presynaptic-events
#6
Mariusz Popek, Bartosz Bobula, Joanna Sowa, Grzegorz Hess, Rafał Polowy, Robert Kuba Filipkowski, Małgorzata Frontczak-Baniewicz, Barbara Zabłocka, Jan Albrecht, Magdalena Zielińska
Neurological symptoms of acute liver failure (ALF) reflect decreased excitatory transmission, but the status of ALF-affected excitatory synapse has not been characterized in detail. We studied the effects of ALF in mouse on synaptic transmission and plasticity ex vivo and its relation to distribution of (i) synaptic vesicles (sv) and (ii) functional synaptic proteins within the synapse. ALF-competent neurological and biochemical changes were induced in mice with azoxymethane (AOM). Electrophysiological characteristics (long-term potentiation, whole-cell recording) as well as synapse ultrastructure were evaluated in the cerebral cortex...
January 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28017832/autosomal-recessive-keratoderma-ichthyosis-deafness-arkid-syndrome-is%C3%A2-caused-by-vps33b-mutations-affecting%C3%A2-rab-protein-interaction-and%C3%A2-collagen-modification
#7
Robert Gruber, Clare Rogerson, Christian Windpassinger, Blerida Banushi, Anna Straatman-Iwanowska, Joanna Hanley, Federico Forneris, Robert Strohal, Peter Ulz, Debra Crumrine, Gopinathan K Menon, Stefan Blunder, Matthias Schmuth, Thomas Müller, Holly Smith, Kevin Mills, Peter Kroisel, Andreas R Janecke, Paul Gissen
In this paper, we report three patients with severe palmoplantar keratoderma associated with ichthyosis and sensorineural deafness. Biallelic mutations were found in VPS33B, encoding VPS33B, a Sec1/Munc18 family protein that interacts with Rab11a and Rab25 proteins and is involved in trafficking of the collagen-modifying enzyme LH3. Two patients were homozygous for the missense variant p.Gly131Glu, whereas one patient was compound heterozygous for p.Gly131Glu and the splice site mutation c.240-1G>C, previously reported in patients with arthrogryposis renal dysfunction and cholestasis syndrome...
December 23, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27988858/sequence-specific-assignment-of-methyl-groups-from-the-neuronal-snare-complex-using-lanthanide-induced-pseudocontact-shifts
#8
Yun-Zu Pan, Bradley Quade, Kyle D Brewer, Monika Szabo, James D Swarbrick, Bim Graham, Josep Rizo
Neurotransmitter release depends critically on the neuronal SNARE complex formed by syntaxin-1, SNAP-25 and synaptobrevin, as well as on other proteins such as Munc18-1, Munc13-1 and synaptotagmin-1. Although three-dimensional structures are available for these components, it is still unclear how they are assembled between the synaptic vesicle and plasma membranes to trigger fast, Ca(2+)-dependent membrane fusion. Methyl TROSY NMR experiments provide a powerful tool to study complexes between these proteins, but assignment of the methyl groups of the SNARE complex is hindered by its limited solubility...
December 2016: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/27911771/stability-folding-dynamics-and-long-range-conformational-transition-of-the-synaptic-t-snare-complex
#9
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...
December 13, 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
#10
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
#11
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
#12
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
#13
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 investigated this question in mouse adrenal chromaffin cells and found 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...
November 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27597757/beyond-the-snare-munc18-1-chaperones-%C3%AE-synuclein
#14
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
#15
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
#16
Nady Braidy, Musthafa Mohamed Essa, Anne Poljak, Subash Selvaraju, Samir Al-Adawi, Thamilarasan Manivasagm, Arokiasamy Justin Thenmozhi, Lezanne Ooi, Perminder Sachdev, Gilles J 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...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27466336/distinct-functions-of-syntaxin-1-in-neuronal-maintenance-synaptic-vesicle-docking-and-fusion-in-mouse-neurons
#17
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
#18
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
#19
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
#20
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
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