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https://www.readbyqxmd.com/read/28220789/stim1-activates-crac-channels-through-rotation-of-the-pore-helix-to-open-a-hydrophobic-gate
#1
Megumi Yamashita, Priscilla S-W Yeung, Christopher E Ing, Beth A McNally, Régis Pomès, Murali Prakriya
Store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels constitute a major pathway for Ca(2+) influx and mediate many essential signalling functions in animal cells, yet how they open remains elusive. Here, we investigate the gating mechanism of the human CRAC channel Orai1 by its activator, stromal interacting molecule 1 (STIM1). We find that two rings of pore-lining residues, V102 and F99, work together to form a hydrophobic gate. Mutations of these residues to polar amino acids produce channels with leaky gates that conduct ions in the resting state...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28178265/computational-investigation-of-sphingosine-kinase-1-sphk1-and-calcium-dependent-erk1-2-activation-downstream-of-vegfr2-in-endothelial-cells
#2
Hojjat Bazzazi, Aleksander S Popel
Vascular endothelial growth factor (VEGF) is a powerful regulator of neovascularization. VEGF binding to its cognate receptor, VEGFR2, activates a number of signaling pathways including ERK1/2. Activation of ERK1/2 is experimentally shown to involve sphingosine kinase 1 (SphK1) activation and its calcium-dependent translocation downstream of ERK1/2. Here we construct a rule-based computational model of signaling downstream of VEGFR2, by including SphK1 and calcium positive feedback mechanisms, and investigate their consequences on ERK1/2 activation...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28167653/orai1-activates-proliferation-of-lymphatic-endothelial-cells-in-response-to-laminar-flow-through-kr%C3%A3-ppel-like-factors-2-and-4
#3
Dongwon Choi, Eunkyung Park, Eunson Jung, Young Jin Seong, Mingu Hong, Sunju Lee, James Burford, Georgina Gyarmati, Janos Peti-Peterdi, Sonal Srikanth, Yousang Gwack, Chester J Koh, Evgenii Boriushkin, Anne Hamik, Alex K Wong, Young-Kwon Hong
RATIONALE: Lymphatic vessels function to drain interstitial fluid from a variety of tissues. Although shear stress generated by fluid flow is known to trigger lymphatic expansion and remodeling, the molecular basis underlying flow-induced lymphatic growth is unknown. OBJECTIVE: We aimed to gain a better understanding of the mechanism by which laminar shear stress activates lymphatic proliferation. METHODS AND RESULTS: Primary endothelial cells from dermal blood and lymphatic vessels (BECs and LECs) were exposed to low-rate steady laminar flow...
February 6, 2017: Circulation Research
https://www.readbyqxmd.com/read/28159636/computational-comparison-of-a-calcium-dependent-jellyfish-protein-apoaequorin-and-calmodulin-cholesterol-in-short-term-memory-maintenance
#4
Gene A Morrill, Adele B Kostellow, Raj K Gupta
Memory reconsolidation and maintenance depend on calcium channels and on calcium/calmodulin-dependent kinases regulating protein turnover in the hippocampus. Ingestion of a jellyfish protein, apoaequorin, reportedly protects and/or improves verbal learning in adults and is currently widely advertised for use by the elderly. Apoaequorin is a member of the EF-hand calcium binding family of proteins that includes calmodulin. Calmodulin-1 (148 residues) differs from Apoaequorin (195 residues) in that it contains four rather than three Ca(2+)-binding sites and three rather than four cholesterol-binding (CRAC, CARC) domains...
January 31, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28130783/the-trpm7-channel-kinase-regulates-store-operated-calcium-entry
#5
Malika Faouzi, Tatiana Kilch, F David Horgen, Andrea Fleig, Reinhold Penner
The Transient receptor potential melastatin 7 (TRPM7) is a protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins through its kinase domain. In this study we present Store-Operated Calcium Entry (SOCE) as a novel target of TRPM7 kinase activity. TRPM7-deficient chicken DT40 B lymphocytes exhibit a strongly impaired SOCE compared to wild type cells due to reduced Calcium Release Activated Calcium (CRAC) currents and independent of potassium channel regulation, membrane potential changes or changes in cell-cycle distribution...
January 28, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28126709/enhanced-store-operated-ca2-influx-and-orai1-expression-in-ventricular-fibroblasts-from-human-failing-heart
#6
Gracious R Ross, Tanvir Bajwa, Stacie Edwards, Larisa Emelyanova, Farhan Rizvi, Ekhson L Holmuhamedov, Paul Werner, Francis X Downey, A Jamil Tajik, Arshad Jahangir
Excessive cardiac fibrosis, characterized by increased collagen-rich extracellular matrix (ECM) deposition, is a major predisposing factor for mechanical and electrical dysfunction in heart failure (HF). The human ventricular fibroblast (hVF) remodeling mechanisms that cause excessive collagen deposition in HF are unclear, although reports suggest a role for [Ca(2+)]i in fibrosis. Therefore, we determined the association of differences in cellular Ca(2+) dynamics and collagen secretion/deposition between hVFs from failing and normal (control) hearts...
January 26, 2017: Biology Open
https://www.readbyqxmd.com/read/28115624/the-g-patch-protein-nf-%C3%AE%C2%BAb-repressing-factor-mediates-the-recruitment-of-the-exonuclease-xrn2-and-activation-of-the-rna-helicase-dhx15-in-human-ribosome-biogenesis
#7
Indira Memet, Carmen Doebele, Katherine E Sloan, Markus T Bohnsack
In eukaryotes, the synthesis of ribosomal subunits, which involves the maturation of the ribosomal (r)RNAs and assembly of ribosomal proteins, requires the co-ordinated action of a plethora of ribosome biogenesis factors. Many of these cofactors remain to be characterized in human cells. Here, we demonstrate that the human G-patch protein NF-κB-repressing factor (NKRF) forms a pre-ribosomal subcomplex with the DEAH-box RNA helicase DHX15 and the 5'-3' exonuclease XRN2. Using UV crosslinking and analysis of cDNA (CRAC), we reveal that NKRF binds to the transcribed spacer regions of the pre-rRNA transcript...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28108030/pore-opening-mechanism-of-crac-channels
#8
REVIEW
Priscilla S-W Yeung, Megumi Yamashita, Murali Prakriya
Three decades ago, James W. Putney Jr. conceptualized the idea of store-operated calcium entry (SOCE) to explain how depletion of endoplasmic reticulum (ER) Ca(2+) stores evokes Ca(2+) influx across the plasma membrane. Since the publication of this highly influential idea, it is now established that SOCE is universal among non-excitable and probably even many types of excitable cells, and contributes to numerous effector functions impacting immunity, muscle contraction, and brain function. The molecules encoding SOCE, the STIM and Orai proteins, are now known and our understanding of how this pathway is activated in response to ER Ca(2+) store depletion has advanced significantly...
December 23, 2016: Cell Calcium
https://www.readbyqxmd.com/read/28104276/optogenetic-toolkit-for-precise-control-of-calcium-signaling
#9
REVIEW
Guolin Ma, Shufan Wen, Lian He, Yun Huang, Youjun Wang, Yubin Zhou
Calcium acts as a second messenger to regulate a myriad of cell functions, ranging from short-term muscle contraction and cell motility to long-term changes in gene expression and metabolism. To study the impact of Ca(2+)-modulated 'ON' and 'OFF' reactions in mammalian cells, pharmacological tools and 'caged' compounds are commonly used under various experimental conditions. The use of these reagents for precise control of Ca(2+) signals, nonetheless, is impeded by lack of reversibility and specificity. The recently developed optogenetic tools, particularly those built upon engineered Ca(2+) release-activated Ca(2+) (CRAC) channels, provide exciting opportunities to remotely and non-invasively modulate Ca(2+) signaling due to their superior spatiotemporal resolution and rapid reversibility...
January 16, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28100609/sterol-binding-by-the-tombusviral-replication-proteins-is-essential-for-replication-in-yeast-and-plants
#10
Kai Xu, Peter D Nagy
: Membranous structures derived from various organelles are important for replication of plus-stranded RNA viruses. Although the important roles of co-opted host proteins in RNA virus replication have been appreciated for a decade, the equally important functions of cellular lipids in virus replication are gaining full attention only recently. Previous works with Tomato bushy stunt tombusvirus (TBSV) in model host yeast have revealed essential roles for phosphatidylethanolamine and sterols in viral replication...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28089266/trpc1-orai1-and-stim1-in-soce-friends-in-tight-spaces
#11
REVIEW
Indu S Ambudkar, Lorena Brito de Souza, Hwei Ling Ong
Store-operated calcium entry (SOCE) is a ubiquitous Ca(2+) entry pathway that is activated in response to depletion of ER-Ca(2+) stores and critically controls the regulation of physiological functions in miscellaneous cell types. The transient receptor potential canonical 1 (TRPC1) is the first member of the TRPC channel subfamily to be identified as a molecular component of SOCE. While TRPC1 has been shown to contribute to SOCE and regulate various functions in many cells, none of the reported TRPC1-mediated currents resembled ICRAC, the highly Ca(2+)-selective store-dependent current first identified in lymphocytes and mast cells...
December 30, 2016: Cell Calcium
https://www.readbyqxmd.com/read/28057422/structure-activity-relationship-study-and-discovery-of-indazole-3-carboxamides-as-calcium-release-activated-calcium-channel-blockers
#12
Sha Bai, Masazumi Nagai, Steffi K Koerner, Aristidis Veves, Lijun Sun
Aberrant activation of mast cells contributes to the development of numerous diseases including cancer, autoimmune disorders, as well as diabetes and its complications. The influx of extracellular calcium via the highly calcium selective calcium-release activated calcium (CRAC) channel controls mast cell functions. Intracellular calcium homeostasis in mast cells can be maintained via the modulation of the CRAC channel, representing a critical point for therapeutic interventions. We describe the structure-activity relationship study (SAR) of indazole-3-carboxamides as potent CRAC channel blockers and their ability to stabilize mast cells...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28043696/regulation-of-crac-channels-by-ca-2-dependent-inactivation
#13
REVIEW
Anant B Parekh
CRAC channels are a major route for Ca(2+) influx in eukaryotic cells. The channels show prominent Ca(2+)-dependent inactivation through two spatially and temporally distinct mechanisms: fast inactivation, which develops over milliseconds and is triggered by Ca(2+) near the mouth of the channel and slow inactivation, which arises over tens of seconds and requires a rise in global cytosolic Ca(2+). Slow inactivation is controlled physiologically by Ca(2+) uptake into mitochondria through the MCU. Site-directed mutagenesis studies on STIM1 and Orai1 have led to new molecular insight into how fast inactivation occurs...
December 16, 2016: Cell Calcium
https://www.readbyqxmd.com/read/28027799/regulation-of-epithelial-ion-transport-in-exocrine-glands-by-store-operated-ca-2-entry
#14
REVIEW
Axel R Concepcion, Stefan Feske
Store-operated Ca(2+) entry (SOCE) is a conserved mechanism of Ca(2+) influx that regulates Ca(2+) signaling in many cell types. SOCE is activated by depletion of endoplasmic reticulum (ER) Ca(2+) stores in response to physiological agonist stimulation. After it was first postulated by J.W. Putney Jr. in 1986, SOCE has been described in a large number of non-excitable cell types including secretory cells of different exocrine glands. Here we discuss the mechanisms by which SOCE controls salt and fluid secretion in exocrine glands, with a special focus on eccrine sweat glands...
December 21, 2016: Cell Calcium
https://www.readbyqxmd.com/read/27983605/effect-of-the-crac-peptide-vlnyyvw-on-mptp-opening-in-rat-brain-and-liver-mitochondria
#15
Tamara Azarashvili, Olga Krestinina, Yulia Baburina, Irina Odinokova, Vladimir Akatov, Igor Beletsky, John Lemasters, Vassilios Papadopoulos
The translocator protein (TSPO; 18 kDa) is a high-affinity cholesterol-binding protein located in the outer membrane of mitochondria. A domain in the C-terminus of TSPO was characterized as the cholesterol recognition/interaction amino acid consensus (CRAC). The ability of the CRAC domain to bind to cholesterol led us to hypothesize that this peptide may participate in the regulation of mitochondrial membrane permeability. Herein, we report the effect of the synthetic CRAC peptide, VLNYYVW, on mitochondrial permeability transition pore (mPTP) opening...
December 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27919988/up-regulation-of-cytoplasmic-cd24-expression-is-associated-with-malignant-transformation-but-favorable-prognosis-of-colorectal-adenocarcinoma
#16
Min-Kyung Yeo, Yong-Moon Lee, In-Ock Seong, Song-Yi Choi, Kwang-Sun Suh, Kyu Sang Song, Choong-Sik Lee, Jin Man Kim, Kyung-Hee Kim
AIM: Cluster of differentiation 24 (CD24) is known to be a putative marker of stem cell and tumor metastasis. This study aimed to verify the clinicopathological value of CD24 expression in colorectal adenocarcinoma (CRAC). MATERIALS AND METHODS: A total of seven whole-tissue sections of malignant polyps including the sequence non-neoplastic colorectal tissue-adenoma-CRAC, 48 adenomas and 161 CRACs arranged as tissue microarray were examined by immunohistochemistry for CD24 protein expression...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27907088/silver-nanoparticle-directed-mast-cell-degranulation-is-mediated-through-calcium-and-pi3k-signaling-independent-of-the-high-affinity-ige-receptor
#17
Nasser B Alsaleh, Indushekhar Persaud, Jared M Brown
Engineered nanomaterial (ENM)-mediated toxicity often involves triggering immune responses. Mast cells can regulate both innate and adaptive immune responses and are key effectors in allergic diseases and inflammation. Silver nanoparticles (AgNPs) are one of the most prevalent nanomaterials used in consumer products due to their antimicrobial properties. We have previously shown that AgNPs induce mast cell degranulation that was dependent on nanoparticle physicochemical properties. Furthermore, we identified a role for scavenger receptor B1 (SR-B1) in AgNP-mediated mast cell degranulation...
2016: PloS One
https://www.readbyqxmd.com/read/27907003/mapping-cholesterol-interaction-sites-on-serotonin-transporter-through-coarse-grained-molecular-dynamics
#18
Mariarosaria Ferraro, Matteo Masetti, Maurizio Recanatini, Andrea Cavalli, Giovanni Bottegoni
Serotonin transporter (SERT) modulates serotonergic signaling via re-uptake of serotonin in pre-synaptic cells. The inclusion in cholesterol-enriched membrane domains is crucial for SERT activity, suggesting a cross-talk between the protein and the sterol. Here, we develop a protocol to identify potential cholesterol interaction sites coupling statistical analysis to multi-microsecond coarse-grained molecular dynamics simulations of SERT in a previously validated raft-like membrane model. Six putative sites were found, including a putative CRAC motif on TM4 and a CARC motif on TM10...
2016: PloS One
https://www.readbyqxmd.com/read/27882542/a-novel-gain-of-function-mutation-in-orai1-causes-late-onset-tubular-aggregate-myopathy-and-congenital-miosis
#19
M Garibaldi, F Fattori, B Riva, C Labasse, G Brochier, P Ottaviani, S Sacconi, E Vizzaccaro, F Laschena, N B Romero, A Genazzani, E Bertini, G Antonini
We present three members of an Italian family affected by tubular aggregate myopathy (TAM) and congenital miosis harboring a novel missense mutation in ORAI1. All patients had a mild, late onset TAM revealed by asymptomatic creatine kinase (CK) elevation and congenital miosis consistent with a Stormorken-like Syndrome, in the absence of thrombocytopathy. Muscle biopsies showed classical histological findings but ultrastructural analysis revealed atypical tubular aggregates (TAs). The whole body muscle magnetic resonance imaging (MRI) showed a similar pattern of muscle involvement that correlated with clinical severity...
October 13, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27870180/complete-relinquishing-of-anaesthetic-conscientiousness-optimisation-and-nuance-crac-on-trial
#20
N Chrimes
No abstract text is available yet for this article.
December 2016: Anaesthesia
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