keyword
MENU ▼
Read by QxMD icon Read
search

Munc13

keyword
https://www.readbyqxmd.com/read/27914778/familial-haemophagocytosis-lymphohisticytosis-type-3-a-case-report
#1
F Kamoun, M Hsairi, V Grandin, S Ben Ameur, G De Saint Basile, M Hachicha
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive disorder of immune regulation. Here, we report on a fatal case of type 3 FHL (FHL3) in a 45-day-old boy. Clinically, the infant presented with fever and hepatosplenomegaly. Biology showed pancytopenia, elevated ferritin, and decreased fibrinogen. Images of hemophagocytosis were found at the bone morrow examination. The diagnosis of FHL type 3 was made by the identification of homozygous mutation in the Munc13-4 gene (UNC13D) located in exon 20: 1822 del 12bp (V608fs)...
November 30, 2016: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
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/27799161/gene-corrected-human-munc13-4-deficient-cd8-t-cells-can-efficiently-restrict-ebv-driven-lymphoproliferation-in-immunodeficient-mice
#3
Tayebeh Soheili, Julie Rivière, Ida Ricciardelli, Amandine Durand, Els Verhoeyen, Anne-Céline Derrien, Chantal Lagresle-Peyrou, Geneviève de Saint Basile, François-Loïc Cosset, Persis Amrolia, Isabelle André-Schmutz, Marina Cavazzana
No abstract text is available yet for this article.
October 31, 2016: Blood
https://www.readbyqxmd.com/read/27798178/differential-expression-of-munc13-2-produces-unique-synaptic-phenotypes-in-the-basolateral-amygdala-of-c57bl-6j-and-dba-2j-mice
#4
Dominic A Gioia, Nancy J Alexander, Brian A McCool
: C57BL/6J (B6) and DBA/2J (D2) mice are well known to differentially express a number of behavioral phenotypes, including anxiety-like behavior, fear conditioning, and drug self-administration. However, the cellular mechanisms contributing to these differences remain unclear. Given the basolateral amygdala (BLA) contributes to these behaviors, we characterized strain-dependent differences in presynaptic and postsynaptic function in BLA neurons by integrating electrophysiological, biochemical, and genetic approaches to identify specific molecular mechanisms...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27733578/rab27a-regulates-gm-csf-dependent-priming-of-neutrophil-exocytosis
#5
Mahalakshmi Ramadass, Jennifer Linda Johnson, Sergio D Catz
Neutrophil secretory proteins are mediators of systemic inflammation in infection, trauma, and cancer. In response to specific inflammatory mediators, neutrophil granules are mobilized and cargo proteins released to modulate the microenvironment of inflammatory sites and tumors. In particular, GM-CSF, a cytokine secreted by several immune, nonimmune, and tumor cells, regulates neutrophil priming and exocytosis. Whereas a comprehensive understanding of this process is necessary to design appropriate anti-inflammatory therapies, the molecular effectors regulating GM-CSF-dependent priming of neutrophil exocytosis are currently unknown...
October 12, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27731902/c2-domain-containing-calcium-sensors-in-neuroendocrine-secretion
#6
REVIEW
Paulo S Pinheiro, Sébastien Houy, Jakob B Sørensen
The molecular mechanisms for calcium-triggered membrane fusion have long been sought for, and detailed models now exist that account for at least some of the functions of the many proteins involved in the process. Key players in the fusion reaction are a group of proteins that, upon binding to calcium, trigger the merger of cargo-filled vesicles with the plasma membrane. Low-affinity, fast-kinetics calcium sensors of the synaptotagmin family - especially synaptotagmin-1 and synaptotagmin-2 - are the main calcium sensors for fast exocytosis triggering in many cell types...
October 12, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27701149/mst1-dependent-vesicle-trafficking-regulates-neutrophil-transmigration-through-the-vascular-basement-membrane
#7
Angela R M Kurz, Monika Pruenster, Ina Rohwedder, Mahalakshmi Ramadass, Kerstin Schäfer, Ute Harrison, Gabriel Gouveia, Claudia Nussbaum, Roland Immler, Johannes R Wiessner, Andreas Margraf, Dae-Sik Lim, Barbara Walzog, Steffen Dietzel, Markus Moser, Christoph Klein, Dietmar Vestweber, Rainer Haas, Sergio D Catz, Markus Sperandio
Neutrophils need to penetrate the perivascular basement membrane for successful extravasation into inflamed tissue, but this process is incompletely understood. Recent findings have associated mammalian sterile 20-like kinase 1 (MST1) loss of function with a human primary immunodeficiency disorder, suggesting that MST1 may be involved in immune cell migration. Here, we have shown that MST1 is a critical regulator of neutrophil extravasation during inflammation. Mst1-deficient (Mst1-/-) neutrophils were unable to migrate into inflamed murine cremaster muscle venules, instead persisting between the endothelium and the basement membrane...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27648472/loss-of-munc13-1-function-causes-microcephaly-cortical-hyperexcitability-and-fatal-myasthenia
#8
Andrew G Engel, Duygu Selcen, Xin-Ming Shen, Margherita Milone, C Michel Harper
OBJECTIVE: To identify the molecular basis of a fatal syndrome of microcephaly, cortical hyperexcitability, and myasthenia. METHODS: We performed clinical and in vitro microelectrode studies of neuromuscular transmission, examined neuromuscular junctions cytochemically and by electron microscopy (EM), and searched for mutations by Sanger and exome sequencing. RESULTS: Neuromuscular transmission was severely compromised by marked depletion of the readily releasable pool of quanta, but the probability of quantal release was normal...
October 2016: Neurology. Genetics
https://www.readbyqxmd.com/read/27558339/molecular-mechanisms-regulating-secretory-organelles-and-endosomes-in-neutrophils-and-their-implications-for-inflammation
#9
REVIEW
Mahalakshmi Ramadass, Sergio D Catz
Neutrophils constitute the first line of cellular defense against invading microorganisms and modulate the subsequent innate and adaptive immune responses. In order to execute a rapid and precise response to infections, neutrophils rely on preformed effector molecules stored in a variety of intracellular granules. Neutrophil granules contain microbicidal factors, the membrane-bound components of the respiratory burst oxidase, membrane-bound adhesion molecules, and receptors that facilitate the execution of all neutrophil functions including adhesion, transmigration, phagocytosis, degranulation, and neutrophil extracellular trap formation...
September 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27537483/fusion-competent-synaptic-vesicles-persist-upon-active-zone-disruption-and-loss-of-vesicle-docking
#10
Shan Shan H Wang, Richard G Held, Man Yan Wong, Changliang Liu, Aziz Karakhanyan, Pascal S Kaeser
In a nerve terminal, synaptic vesicle docking and release are restricted to an active zone. The active zone is a protein scaffold that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Here, we generated conditional knockout mice removing the active zone proteins RIM and ELKS, which additionally led to loss of Munc13, Bassoon, Piccolo, and RIM-BP, indicating disassembly of the active zone. We observed a near-complete lack of synaptic vesicle docking and a strong reduction in vesicular release probability and the speed of exocytosis, but total vesicle numbers, SNARE protein levels, and postsynaptic densities remained unaffected...
August 17, 2016: Neuron
https://www.readbyqxmd.com/read/27528604/the-vesicle-priming-factor-caps-functions-as-a-homodimer-via-c2-domain-interactions-to-promote-regulated-vesicle-exocytosis
#11
Matt Petrie, Joseph Esquibel, Greg Kabachinski, Stephanie Maciuba, Hirohide Takahashi, J Michael Edwardson, Thomas F J Martin
Neurotransmitters and peptide hormones are secreted by regulated vesicle exocytosis. CAPS (also known as CADPS) is a 145-kDa cytosolic and peripheral membrane protein required for vesicle docking and priming steps that precede Ca(2+)-triggered vesicle exocytosis. CAPS binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and SNARE proteins and is proposed to promote SNARE protein complex assembly for vesicle docking and priming. We characterized purified soluble CAPS as mainly monomer in equilibrium with small amounts of dimer...
September 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27454932/photoswitchable-diacylglycerols-enable-optical-control-of-protein-kinase-c
#12
James Allen Frank, Dmytro A Yushchenko, David J Hodson, Noa Lipstein, Jatin Nagpal, Guy A Rutter, Jeong-Seop Rhee, Alexander Gottschalk, Nils Brose, Carsten Schultz, Dirk Trauner
Increased levels of the second messenger lipid diacylglycerol (DAG) induce downstream signaling events including the translocation of C1-domain-containing proteins toward the plasma membrane. Here, we introduce three light-sensitive DAGs, termed PhoDAGs, which feature a photoswitchable acyl chain. The PhoDAGs are inactive in the dark and promote the translocation of proteins that feature C1 domains toward the plasma membrane upon a flash of UV-A light. This effect is quickly reversed after the termination of photostimulation or by irradiation with blue light, permitting the generation of oscillation patterns...
September 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27408432/familial-hemophagocytic-lymphohistiocytosis-due-to-mutation-of-unc13d-gene
#13
Prabhas Prasun Giri, Nirmoy Biswas, Swati Chakravarty
Hemophagocytic lymphohistiocytosis (HLH) are basically a heterogenous group of clinical syndromes, characterised by activation and non-malignant proliferation of benign histiocytes i.e. lymphocytes and macrophages, leading to a cytokine storm that accounts for the fever, organomegaly and multi-organ dysfunction. Two types of HLH are described, either due to known genetic defect (familial HLH/FHL) or due to some acquired cause either infection or rheumatological diseases. Here we present a case of a 3 months old baby, admitted with fever, hepatosplenomegaly and cytopenia and ultimately was diagnosed to be a case of Familial HLH type 3 due to defect in UNC13D gene as a result of compound heterozygous for two nonsense mutation resulting in the Munc13-4 protein defect...
June 2016: Indian Journal of Hematology & Blood Transfusion
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/27154627/distinct-modes-of-endocytotic-presynaptic-membrane-and-protein-uptake-at-the-calyx-of-held-terminal-of-rats-and-mice
#15
Yuji Okamoto, Noa Lipstein, Yunfeng Hua, Kun-Han Lin, Nils Brose, Takeshi Sakaba, Mitsuharu Midorikawa
Neurotransmitter is released at synapses by fusion of synaptic vesicles with the plasma membrane. To sustain synaptic transmission, compensatory retrieval of membranes and vesicular proteins is essential. We combined capacitance measurements and pH-imaging via pH-sensitive vesicular protein marker (anti-synaptotagmin2-cypHer5E), and compared the retrieval kinetics of membranes and vesicular proteins at the calyx of Held synapse. Membrane and Syt2 were retrieved with a similar time course when slow endocytosis was elicited...
2016: ELife
https://www.readbyqxmd.com/read/27091977/phosphorylation-of-synaptotagmin-1-controls-a-post-priming-step-in-pkc-dependent-presynaptic-plasticity
#16
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/27079884/intracellular-trafficking-localization-and-mobilization-of-platelet-borne-thiol-isomerases
#17
Marilena Crescente, Fred G Pluthero, Ling Li, Richard W Lo, Tony G Walsh, Michael P Schenk, Lisa M Holbrook, Silvia Louriero, Marfoua S Ali, Sakthivel Vaiyapuri, Hervé Falet, Ian M Jones, Alastair W Poole, Walter H A Kahr, Jonathan M Gibbins
OBJECTIVE: Thiol isomerases facilitate protein folding in the endoplasmic reticulum, and several of these enzymes, including protein disulfide isomerase and ERp57, are mobilized to the surface of activated platelets, where they influence platelet aggregation, blood coagulation, and thrombus formation. In this study, we examined the synthesis and trafficking of thiol isomerases in megakaryocytes, determined their subcellular localization in platelets, and identified the cellular events responsible for their movement to the platelet surface on activation...
June 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27016801/a-novel-rab27a-mutation-binds-melanophilin-but-not-munc13-4-causing-immunodeficiency-without-albinism
#18
Petra Netter, Sanny K Chan, Pinaki P Banerjee, Linda Monaco-Shawver, Lenora M Noroski, Imelda C Hanson, Lisa R Forbes, Emily M Mace, Javier Chinen, H Bobby Gaspar, Patrick Sleiman, Hakon Hakonarson, Christoph Klein, Mohammad S Ehlayel, Jordan S Orange
No abstract text is available yet for this article.
August 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/26987330/impairment-of-immune-function-in-children-with-familial-hemophagocytic-lymphohistiocytosis
#19
K Popko, J Jasińska, E Górska, U Demkow, W Balwierz, L Maciejka-Kembłowska, W Badowska, J Wachowiak, K Drabko, I Malinowska
Hemophagocytic lymphohistiocytosis (HLH) is a severe systemic syndrome associated with hyperactivation of macrophages and impaired regulation of the immune system. Two forms of HLH are currently recognized: genetically determined or familial (FHLH), and secondarily developed in the course of primary diseases, like autoimmune disorders, rheumatoid disorders, cancers, or infections. In the Polish population, FHLH is rather rare. The aim of the present study was to assess the immune function in a group of children with clinical symptoms suggesting FHLH...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/26959078/1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-induced-parkinson-s-disease-in-zebrafish
#20
Nukala Sarath Babu, Ch Lakshmi N Murthy, Sameera Kakara, Rahul Sharma, Cherukuvada V Brahmendra Swamy, Mohammed M Idris
Parkinson's disease (PD) is the most common age associated neurodegenerative disease, which has been extensively studied for its etiology and phenotype. PD has been widely studied in alternate model system such as rodents towards understanding the role of neurotoxin by inducing PD. This study is aimed to understand the biomechanism of PD in zebrafish model system induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The phenotype and role of various genes and proteins for Parkinsonism were tested and evaluated in this study using behavior, molecular and proteomic approaches...
May 2016: Proteomics
keyword
keyword
12117
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"