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Calmodulin

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https://www.readbyqxmd.com/read/28087622/calmodulin-limits-pathogenic-na-channel-persistent-current
#1
Haidun Yan, Chaojian Wang, Steven O Marx, Geoffrey S Pitt
Increased "persistent" current, caused by delayed inactivation, through voltage-gated Na(+) (NaV) channels leads to cardiac arrhythmias or epilepsy. The underlying molecular contributors to these inactivation defects are poorly understood. Here, we show that calmodulin (CaM) binding to multiple sites within NaV channel intracellular C-terminal domains (CTDs) limits persistent Na(+) current and accelerates inactivation across the NaV family. Arrhythmia or epilepsy mutations located in NaV1.5 or NaV1.2 channel CTDs, respectively, reduce CaM binding either directly or by interfering with CTD-CTD interchannel interactions...
January 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28079567/cardiac-calcium-release-channel-ryanodine-receptor-2-regulation-by-halogenated-anesthetics
#2
Derek R Laver, John Attia, Christopher Oldmeadow, Anthony W Quail
BACKGROUND: Halogenated anesthetics activate cardiac ryanodine receptor 2-mediated sarcoplasmic reticulum Ca release, leading to sarcoplasmic reticulum Ca depletion, reduced cardiac function, and providing cell protection against ischemia-reperfusion injury. Anesthetic activation of ryanodine receptor 2 is poorly defined, leaving aspects of the protective mechanism uncertain. METHODS: Ryanodine receptor 2 from the sheep heart was incorporated into artificial lipid bilayers, and their gating properties were measured in response to five halogenated anesthetics...
January 12, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28077617/calcineurin-the-ca2-dependent-phosphatase-regulates-rga2-a-cdc42-gtpase-activating-protein-to-modulate-pheromone-signaling
#3
Nina Ly, Martha S Cyert
Calcineurin, the conserved Ca(2+)/calmodulin-activated phosphatase, is required for viability during prolonged exposure to pheromone, and acts through multiple substrates to down regulate yeast pheromone signaling. Calcineurin regulates Dig2 and Rod1/Art4 to inhibit mating-induced gene expression and activate receptor internalization, respectively. Recent systematic approaches identified Rga2, a GTPase activating protein (GAP) for the Cdc42 Rho-type GTPase, as a calcineurin substrate. Here, we establish a physiological context for this regulation, and show that calcineurin dephosphorylates and positively regulates Rga2 during pheromone signaling...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28077321/camkii%C3%AE-subtypes-differentially-regulate-infarct-formation-following-ex-vivo-myocardial-ischemia-reperfusion-through-nf-%C3%AE%C2%BAb-and-tnf-%C3%AE
#4
Charles B B Gray, Takeshi Suetomi, Sunny Xiang, Erik A Blackwood, Christopher C Glembotski, Shigeki Miyamoto, B Daan Westenbrink, Joan Heller Brown
Deletion of Ca(2+/)calmodulin-dependent protein kinase II delta (CaMKIIδ) has been shown to protect against in vivo ischemia/reperfusion (I/R) injury. It remains unclear which CaMKIIδ isoforms and downstream mechanisms are responsible for the salutary effects of CaMKIIδ gene deletion. In this study we sought to compare the roles of the CaMKIIδB and CaMKIIδC subtypes and the mechanisms by which they contribute to ex vivo I/R damage. WT, CaMKIIδKO, and mice expressing only CaMKIIδB or δC were subjected to ex vivo global ischemia for 25min followed by reperfusion...
January 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28076819/full-spectral-multiplexing-of-bioluminescence-resonance-energy-transfer-in-three-trpv-channels
#5
Hermanus Johannes Ruigrok, Guillaume Shahid, Bertrand Goudeau, Florence Poulletier de Gannes, Emmanuelle Poque-Haro, Annabelle Hurtier, Isabelle Lagroye, Pierre Vacher, Stéphane Arbault, Neso Sojic, Bernard Veyret, Yann Percherancier
Multiplexed bioluminescence resonance energy transfer (BRET) assays were developed to monitor the activation of several functional transient receptor potential (TRP) channels in live cells and in real time. We probed both TRPV1 intramolecular rearrangements and its interaction with Calmodulin (CaM) under activation by chemical agonists and temperature. Our BRET study also confirmed that: (1) capsaicin and heat promoted distinct transitions, independently coupled to channel gating, and that (2) TRPV1 and Ca(2+)-bound CaM but not Ca(2+)-free CaM were preassociated in resting live cells, while capsaicin activation induced both the formation of more TRPV1/CaM complexes and conformational changes...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28070852/functional-characterization-of-the-powdery-mildew-susceptibility-gene-smmlo1-in-eggplant-solanum-melongena-l
#6
Valentina Bracuto, Michela Appiano, Luigi Ricciardi, Deniz Göl, Richard G F Visser, Yuling Bai, Stefano Pavan
Eggplant (Solanum melongena L.) is one of the most important vegetables among the Solanaceae and can be a host to fungal species causing powdery mildew (PM) disease. Specific homologs of the plant Mildew Locus O (MLO) gene family are PM susceptibility factors, as their loss of function results in a recessive form of resistance known as mlo resistance. In a previous work, we isolated the eggplant MLO homolog SmMLO1. SmMLO1 is closely related to MLO susceptibility genes characterized in other plant species. However, it displays a peculiar non-synonymous substitution that leads to a T → M amino acid change at protein position 422, in correspondence of the MLO calmodulin-binding domain...
January 9, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28066144/intravenous-administration-of-piceatannol-an-arginase-inhibitor-improves-endothelial-dysfunction-in-aged-mice
#7
Minh Cong Nguyen, Sungwoo Ryoo
Advanced age is one of the risk factors for vascular diseases that are mainly caused by impaired nitric oxide (NO) production. It has been demonstrated that endothelial arginase constrains the activity of endothelial nitric oxide synthase (eNOS) and limits NO generation. Hence, arginase inhibition is suggested to be vasoprotective in aging. In this study, we examined the effects of intravenous injection of Piceatannol, an arginase inhibitor, on aged mice. Our results show that Piceatannol administration reduced the blood pressure in aged mice by inhibiting arginase activity, which was associated with NO production and reactive oxygen species generation...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28065796/ischaemia-and-excitotoxicity-induced-camkii-mediated-neuronal-cell-death-the-relative-roles-of-camkii-autophosphorylation-at-t286-and-t253
#8
John A P Rostas, Alexander Hoffman, Lucy A Murtha, Debbie Pepperall, Damian D McLeod, Phillip W Dickson, Neil J Spratt, Kathryn A Skelding
Ischaemia/excitotoxicity produces persistent activation of CaMKII (Ca(2+)-calmodulin stimulated protein kinase II) that initiates cell death. This study investigated the involvement of CaMKII phosphorylation at T286 and T253 in producing this persistent activation. In T286A-αCaMKII transgenic mice that lack the ability to phosphorylate αCaMKII at T286, transient occlusion of the middle cerebral artery for 90 min resulted in no significant difference in infarct size compared to normal littermate controls...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28062709/trifluoperazine-a-well-known-antipsychotic-inhibits-glioblastoma-invasion-by-binding-to-calmodulin-and-disinhibiting-calcium-release-channel-ip3r
#9
Seokmin Kang, Jinpyo Hong, Jung Moo Lee, Hyo Eun Moon, Borami Jeon, Jungil Choi, Nal Ae Yoon, Sun Ha Paek, Eun Joo Roh, C Justin Lee, Sang Soo Kang
Calcium (Ca(2+)) signaling is an important signaling process, implicated in cancer cell proliferation and motility of the deadly glioblastomas that aggressively invade neighboring brain tissue. We have previously demonstrated that caffeine blocks glioblastoma invasion and extends survival by inhibiting Ca(2+) release channel inositol 1,4,5-trisphosphate receptor (IP3R) subtype 3. Trifluoperazine (TFP) is an FDA-approved antipsychotic drug for schizophrenia. Interestingly, TFP has been recently reported to show a strong anticancer effect on lung cancer, hepatocellular carcinoma, and T-cell lymphoma...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28062321/tom9-2-is-a-calmodulin-binding-protein-critical-for-tom-complex-assembly-but-not-for-mitochondrial-protein-import-in-arabidopsis-thaliana
#10
Nargis Parvin, Chris Carrie, Isabelle Pabst, Antonia Läßer, Debabrata Laha, Melanie Paul, Peter Geigenberger, Ralf Heermann, Kirsten Jung, Ute C Vothknecht, Fatima Chigri
The translocon on the outer membrane of mitochondria (TOM) facilitates import of nuclear encoded proteins. The principal machinery seems conserved in eukaryotes, however, divergence in composition and structure of TOM components has been observed between mammals, yeast and plants. TOM9, the plant homologue of yeast Tom22, is significantly smaller due to a truncation in the cytosolic receptor domain and its precise function is not understood. Here we provide evidences that TOM9.2 from Arabidopsis thaliana is involved in the formation of the mature TOM complex, most likely by influencing the assembly of the pore-forming subunit TOM40...
January 3, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28059801/repeated-anodal-transcranial-direct-current-stimulation-induces-neural-plasticity-associated-gene-expression-in-the-rat-cortex-and-hippocampus
#11
Min Sun Kim, Ho Koo, Sang Who Han, Walter Paulus, Michael A Nitsche, Yun-Hee Kim, Jin A Yoon, Yong-Il Shin
BACKGROUND: Anodal transcranial direct current stimulation (A-tDCS) induces a long-lasting increase in cortical excitability that can increase gene transcription in the brain. OBJECTIVE: The purpose of this study was to evaluate the expression of genes related to activity-dependent neuronal plasticity in the sensorimotor cortex and hippocampus of young Sprague-Dawley rats following A-tDCS. METHODS: We applied A-tDCS over the right sensorimotor cortex epicranially with a circular electrode (3 mm diameter) at 250 μA for 20 min per day for 7 consecutive days...
January 4, 2017: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/28059704/cooperative-and-acute-inhibitionby-multiple-c-terminal-motifs-of-l-type-ca-2-channels
#12
Nan Liu, Yaxiong Yang, Lin Ge, Min Liu, Henry M Colecraft, Xiaodong Liu
Inhibitions and antagonists of L-type Ca(2+) channels are important to both research and therapeutics. Here, we report C-terminus mediated inhibition (CMI) for CaV1.3 that multiple motifs coordinate to tune down Ca(2+) current and Ca(2+) influx toward the lower limits determined by end-stage CDI (Ca(2+)-dependent inactivation). Among IQV (preIQ3-IQ domain), PCRD and DCRD (proximal or distal C-terminal regulatory domain), spatial closeness of any two modules, e.g., by constitutive fusion, facilitates the trio to form the complex, compete against calmodulin, and alter the gating...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28059571/presynaptic-calmodulin-targets-lessons-from-structural-proteomics
#13
Noa Lipstein, Melanie Göth, Christine Piotrowski, Kevin Pagel, Andrea Sinz, Olaf Jahn
Calmodulin (CaM) is a highly conserved Ca(2+)-binding protein that is exceptionally abundant in the brain. In the presynaptic compartment of neurons, CaM transduces changes in Ca(2+) concentration into the regulation of synaptic transmission dynamics. Areas covered: We review selected literature including published CaM interactor screens and outline established and candidate presynaptic CaM targets. We present a workflow of biochemical and structural proteomic methods that were used to identify and characterize the interactions between CaM and Munc13 proteins...
January 6, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28055297/a-strategy-to-identify-linker-based-modules-for-the-allosteric-regulation-of-antibody-antigen-binding-affinities-of-different-scfvs
#14
Sarah-Jane Kellmann, Stefan Dübel, Holger Thie
Antibody single-chain variable fragments (scFvs) are used in a variety of applications, such as for research, diagnosis and therapy. Essential for these applications is the extraordinary specificity, selectivity and affinity of antibody paratopes, which can also be employed for efficient protein purification. However, this use is hampered by the high affinity for the protein to be purified because harsh elution conditions, which may impair folding, integrity or viability of the eluted biomaterials, are typically required...
January 5, 2017: MAbs
https://www.readbyqxmd.com/read/28053034/simultaneous-loss-of-nckx4-and-cng-channel-desensitization-impairs-olfactory-sensitivity
#15
Christopher H Ferguson, Haiqing Zhao
: In vertebrate olfactory sensory neurons (OSNs), Ca(2+) plays key roles in both mediating and regulating the olfactory response. Ca(2+) enters OSN cilia during the response through the olfactory cyclic nucleotide-gated (CNG) channel and stimulates a depolarizing chloride current by opening the olfactory Ca(2+)-activated chloride channel to amplify the response. Ca(2+) also exerts negative regulation on the olfactory transduction cascade, through mechanisms that include reducing the CNG current by desensitizing the CNG channel via Ca(2+)/calmodulin (CaM), to reduce the response...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28050053/aspergillus-section-nidulantes-formerly-emericella-polyphasic-taxonomy-chemistry-and-biology
#16
A J Chen, J C Frisvad, B D Sun, J Varga, S Kocsubé, J Dijksterhuis, D H Kim, S-B Hong, J Houbraken, R A Samson
Aspergillus section Nidulantes includes species with striking morphological characters, such as biseriate conidiophores with brown-pigmented stipes, and if present, the production of ascomata embedded in masses of Hülle cells with often reddish brown ascospores. The majority of species in this section have a sexual state, which were named Emericella in the dual name nomenclature system. In the present study, strains belonging to subgenus Nidulantes were subjected to multilocus molecular phylogenetic analyses using internal transcribed spacer region (ITS), partial β-tubulin (BenA), calmodulin (CaM) and RNA polymerase II second largest subunit (RPB2) sequences...
June 2016: Studies in Mycology
https://www.readbyqxmd.com/read/28049192/combined-memantine-and-donepezil-treatment-improves-behavioral-and-psychological-symptoms-of-dementia-like-behaviors-in-olfactory-bulbectomized-mice
#17
Yasushi Yabuki, Kazuya Matsuo, Koga Hirano, Yasuharu Shinoda, Shigeki Moriguchi, Kohji Fukunaga
Memantine, an uncompetitive N-methyl-D-aspartate receptor antagonist, and the cholinesterase inhibitor, donepezil, are approved in most countries for treating moderate-to-severe Alzheimer's disease (AD). These drugs have different molecular targets; thus, it is expected that the effects of combined treatment would be synergistic. Some reports do show memantine/donepezil synergy in ameliorating cognition in AD model animals, but their combined effects on behavioral and psychological symptoms of dementia (BPSD)-like behaviors have not been addressed...
January 4, 2017: Pharmacology
https://www.readbyqxmd.com/read/28045382/solution-of-the-structure-of-a-calmodulin-peptide-complex-in-a-novel-configuration-from-a-variably-twinned-data-set
#18
Jacob Pearson Keller
Structure determination of conformationally variable proteins can prove challenging even when many possible molecular-replacement (MR) search models of high sequence similarity are available. Calmodulin (CaM) is perhaps the best-studied archetype of these flexible proteins: while there are currently ∼450 structures of significant sequence similarity available in the Protein Data Bank (PDB), novel conformations of CaM and complexes thereof continue to be reported. Here, the details of the solution of a novel peptide-CaM complex structure by MR are presented, in which only one MR solution of marginal quality was found despite the use of 120 different search models, an exclusivity enhanced by the presence of a high degree of hemihedral twinning (overall refined twin fraction = 0...
January 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28036267/microrna-603-acts-as-a-tumor-suppressor-and-inhibits-triple-negative-breast-cancer-tumorigenesis-by-targeting-elongation-factor-2-kinase
#19
Recep Bayraktar, Martin Pichler, Pinar Kanlikilicer, Cristina Ivan, Emine Bayraktar, Nermin Kahraman, Burcu Aslan, Serpil Oguztuzun, Mustafa Ulasli, Ahmet Arslan, George Calin, Gabriel Lopez-Berestein, Bulent Ozpolat
Triple negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by the absence of defined molecular targets, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and is associated with high rates of relapse and distant metastasis despite surgery and adjuvant chemotherapy. The lack of effective targeted therapies for TNBC represents an unmet therapeutic challenge. Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical calcium/calmodulin-dependent serine/threonine kinase that promotes TNBC tumorigenesis, progression, and drug resistance, representing a potential novel molecular target...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032992/cationic-amphiphilic-tris-cyclometalated-iridium-iii-complexes-induce-cancer-cell-death-via-interaction-with-ca-2-calmodulin-complex
#20
Yosuke Hisamatsu, Nozomi Suzuki, Abdullah-Al Masum, Ai Shibuya, Ryo Abe, Akira Sato, Sei-Ichi Tanuma, Shin Aoki
In our previous paper, we reported on the preparation of some cationic amphiphilic Ir complexes (2c, 2d) containing KKGG peptides that induce and detect cell death of Jurkat cells. Mechanistic studies suggest that 2c interacts with anionic molecules and/or membrane receptors on the cell surface to trigger an intracellular Ca(2+) response, resulting in the induction of cell death, accompanied by membrane disruption. We have continued the studies of cell death of Jurkat cells induced by 2c and found that xestospongin C, a selective inhibitor of an inositol 1,4,5-trisphosphate receptor located on the endoplasmic reticulum (ER), reduces the cytotoxicity of 2c, suggesting that 2c triggers the release of Ca(2+) from the ER, leading to an increase in the concentration of cytosolic Ca(2+), thus inducing cell death...
December 29, 2016: Bioconjugate Chemistry
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