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https://www.readbyqxmd.com/read/27911714/regulation-of-the-phosphatase-pp2b-by-protein-protein-interactions
#1
REVIEW
Patrick J Nygren, John D Scott
Protein dephosphorylation is important for regulating cellular signaling in a variety of contexts. Protein phosphatase-2B (PP2B), or calcineurin, is a widely expressed serine/threonine phosphatase that acts on a large cross section of potential protein substrates when activated by increased levels of intracellular calcium in concert with calmodulin. PxIxIT and LxVP targeting motifs are important for maintaining specificity in response to elevated calcium. In the present study, we describe the mechanism of PP2B activation, discuss its targeting by conserved binding motifs and review recent advances in the understanding of an A-kinase anchoring protein 79/PP2B/protein kinase A complex's role in synaptic long-term depression...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27908611/entorhinal-principal-neurons-mediate-brain-stimulation-treatments-for-epilepsy
#2
Zhenghao Xu, Yi Wang, Bin Chen, Cenglin Xu, Xiaohua Wu, Ying Wang, Shihong Zhang, Weiwei Hu, Shuang Wang, Yi Guo, Xiangnan Zhang, Jianhong Luo, Shumin Duan, Zhong Chen
Brain stimulation is an alternative treatment for epilepsy. However, the neuronal circuits underlying its mechanisms remain obscure. We found that optogenetic activation (1Hz) of entorhinal calcium/calmodulin-dependent protein kinase II α (CaMKIIα)-positive neurons, but not GABAergic neurons, retarded hippocampal epileptogenesis and reduced hippocampal seizure severity, similar to that of entorhinal low-frequency electrical stimulation (LFES). Optogenetic inhibition of entorhinal CaMKIIα-positive neurons blocked the antiepileptic effect of LFES...
November 23, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27906053/attenuated-ca-2-release-in-a-mouse-model-of-limb-girdle-muscular-dystrophy-2a
#3
Marino DiFranco, Irina Kramerova, Julio L Vergara, Melissa Jan Spencer
BACKGROUND: Mutations in CAPN3 cause limb girdle muscular dystrophy type 2A (LGMD2A), a progressive muscle wasting disease. CAPN3 is a non-lysosomal, Ca-dependent, muscle-specific proteinase. Ablation of CAPN3 (calpain-3 knockout (C3KO) mice) leads to reduced ryanodine receptor (RyR1) expression and abnormal Ca2+/calmodulin-dependent protein kinase II (Ca-CaMKII)-mediated signaling. We previously reported that Ca(2+) release measured by fura2-FF imaging in response to single action potential stimulation was reduced in old C3KO mice; however, the use of field stimulation prevented investigation of the mechanisms underlying this impairment...
February 24, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905406/differential-roles-for-l-type-calcium-channel-subtypes-in-alcohol-dependence
#4
Stefanie Uhrig, David Vandael, Andrea Marcantoni, Nina Dedic, Ainhoa Bilbao, Miriam A Vogt, Natalie Hirth, Laura Broccoli, Rick E Bernardi, Kai Schönig, Peter Gass, Dusan Bartsch, Rainer Spanagel, Jan M Deussing, Wolfgang H Sommer, Emilio Carbone, Anita C Hansson
It has previously been shown that the inhibition of L-type calcium channels (LTCCs) decreases alcohol consumption, although the contribution of the central LTCC subtypes Cav1.2 and Cav1.3 remains unknown. Here, we determined changes in Cav1.2 (Cacna1c) and Cav1.3 (Cacna1d) mRNA and protein expression in alcohol dependent rats during protracted abstinence and naïve controls using in situ hybridization and Western Blot analysis. Functional validation was obtained by electrophysiological recordings of calcium currents in dissociated hippocampal pyramidal neurons...
December 1, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27904490/antidepressant-effect-of-electroacupuncture-regulates-signal-targeting-in-the-brain-and-increases-brain-derived-neurotrophic-factor-levels
#5
Dong-Mei Duan, Ya Tu, Ping Liu, Shuang Jiao
Electroacupuncture improves depressive behavior faster and with fewer adverse effects than antidepressant medication. However, the antidepressant mechanism of electroacupuncture remains poorly understood. Here, we established a rat model of chronic unpredicted mild stress, and then treated these rats with electroacupuncture at Yintang (EX-HN3) and Baihui (DU20) with sparse waves at 2 Hz and 0.6 mA for 30 minutes, once a day. We found increased horizontal and vertical activity, and decreased immobility time, at 2 and 4 weeks after treatment...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27900493/mining-the-cicer-arietinum-genome-for-the-mildew-locus-o-mlo-gene-family-and-comparative-evolutionary-analysis-of-the-mlo-genes-from-medicago-truncatula-and-some-other-plant-species
#6
Reena Deshmukh, V K Singh, Brahma Deo Singh
The mildew locus O (Mlo) gene family is ubiquitous in land plants. Some members of this gene family are involved in negative regulation of powdery mildew resistance, while others are involved in several other biological functions. Mlo proteins have characteristic seven transmembrane domains and a calmodulin-binding domain at their C-termini, and are associated with plasma membrane. The Mlo gene family has been studied in several economically important cereals, but little information is available on this gene family in the important legumes, Medicago truncatula Gaertn...
November 30, 2016: Journal of Plant Research
https://www.readbyqxmd.com/read/27899032/proteomic-profiling-of-the-spinal-cord-in-als-decreased-atp5d-levels-suggest-synaptic-dysfunction-in-als-pathogenesis
#7
Jooyeon Engelen-Lee, Anna M Blokhuis, Wim G M Spliet, R Jeroen Pasterkamp, Eleonora Aronica, Jeroen A A Demmers, Roel Broekhuizen, Giovanni Nardo, Niels Bovenschen, Leonard H Van Den Berg
BACKGROUND: We aimed to gain new insights into the pathogenesis of sporadic ALS (sALS) through a comprehensive proteomic analysis. METHODS: Protein profiles of the anterior and posterior horn in post-mortem spinal cord samples of 10 ALS patients and 10 controls were analysed using 2D-differential gel electrophoresis. The identified protein spots with statistically significant level changes and a spot ratio >2.0 were analysed by LC-MS/MS. RESULTS: In the posterior horn only 3 proteins were differentially expressed...
November 29, 2016: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/27897225/calmodulin-interacts-with-rab3d-and-modulates-osteoclastic-bone-resorption
#8
Sipin Zhu, Shek Man Chim, Taksum Cheng, Estabelle Ang, Benjamin Ng, Baysie Lim, Kai Chen, Heng Qiu, Jennifer Tickner, Huazi Xu, Nathan Pavlos, Jiake Xu
Calmodulin is a highly versatile protein that regulates intracellular calcium homeostasis and is involved in a variety of cellular functions including cardiac excitability, synaptic plasticity and signaling transduction. During osteoclastic bone resorption, calmodulin has been reported to concentrate at the ruffled border membrane of osteoclasts where it is thought to modulate bone resorption activity in response to calcium. Here we report an interaction between calmodulin and Rab3D, a small exocytic GTPase and established regulator osteoclastic bone resorption...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895024/the-role-of-calcium-calmodulin-dependent-protein-kinase-ii-activation-in-hypertrophic-cardiomyopathy
#9
EDITORIAL
Jil C Tardiff
No abstract text is available yet for this article.
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27894086/the-anti-tumor-drug-2-hydroxyoleic-acid-minerval-stimulates-signaling-and-retrograde-transport
#10
Maria L Torgersen, Tove Irene Klokk, Simona Kavaliauskiene, Christian Klose, Kai Simons, Tore Skotland, Kirsten Sandvig
2-hydroxyoleic acid (OHOA, Minerval®) is an example of a substance used for membrane lipid therapy, where the cellular membranes rather than specific proteins constitute the therapeutical target. OHOA is thought to mediate its anti-tumor effect by affecting the biophysical properties of membranes, which leads to altered recruitment and activation of amphitropic proteins, altered cellular signaling, and eventual cell death. Little is known about the initial signaling events upon treatment with OHOA, and whether the altered membrane properties would have any impact on the dynamic intracellular transport system...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889915/constitutive-regulation-of-the-glutamate-aspartate-transporter-eaat1-by-calcium-calmodulin-dependent-protein-kinase-ii
#11
Aarti R Chawla, Derrick E Johnson, Agnes S Zybura, Benjamin P Leeds, Ross M Nelson, Andy Hudmon
Glutamate clearance by astrocytes is an essential part of normal excitatory neurotransmission. Failure to adapt or maintain low levels of glutamate in the central nervous system is associated with multiple acute and chronic neurodegenerative diseases. The primary excitatory amino acid transporters in human astrocytes are EAAT1 and EAAT2 (GLAST and GLT-1 respectively in rodents). While the inhibition of calcium/calmodulin-dependent kinase (CaMKII), a ubiquitously-expressed serine/threonine protein kinase, results in diminished glutamate uptake in cultured primary rodent astrocytes (Ashpole et al...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27888323/the-calmodulin-gene-in-neurospora-crassa-is-required-for-normal-vegetative-growth-ultraviolet-survival-and-sexual-development
#12
Vijya Laxmi, Ranjan Tamuli
We isolated a Neurospora crassa mutant of the calmodulin (cmd) gene using repeat-induced point mutation and studied its phenotypes. The cmd (RIP) mutant showed a defect in growth, reduced aerial hyphae, decreased carotenoid accumulation, a severe reduction in viability upon ultraviolet (UV) irradiation, and a fertility defect. Moreover, meiotic silencing of the cmd gene resulted in a barren phenotype. In addition, we also performed site-directed mutational analysis of the calcium/calmodulin-dependent kinase-2 (Ca(2+)/CaMK-2), a target of the CaM protein encoded by the cmd gene...
November 25, 2016: Archives of Microbiology
https://www.readbyqxmd.com/read/27882454/portraying-the-effect-of-calcium-binding-proteins-on-cytosolic-calcium-concentration-distribution-fractionally-in-nerve-cells
#13
Brajesh Kumar Jha, Hardik Joshi, Devanshi D Dave
Nerve cells like neurons and astrocytes in central nervous system (CNS) take part in the signaling process which means the transformation of the information from one cell to another via signals. The signaling process is affected by various external parameters like buffers calcium-binding proteins, voltage-gated calcium channel. In the present paper, the role of buffers in the cytoplasmic calcium concentration distribution is shown. The elicitation in calcium concentration is due to the presence of lower amount calcium-binding proteins which can be shown graphically...
November 23, 2016: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/27881952/tissue-type-plasminogen-activator-tpa-modulates-the-postsynaptic-response-of-cerebral-cortical-neurons-to-the-presynaptic-release-of-glutamate
#14
Valerie Jeanneret, Fang Wu, Paola Merino, Enrique Torre, Ariel Diaz, Lihong Cheng, Manuel Yepes
Tissue-type plasminogen activator (tPA) is a serine proteinase released by the presynaptic terminal of cerebral cortical neurons following membrane depolarization (Echeverry et al., 2010). Recent studies indicate that the release of tPA triggers the synaptic vesicle cycle and promotes the exocytosis (Wu et al., 2015) and endocytic retrieval (Yepes et al., 2016) of glutamate-containing synaptic vesicles. Here we used electron microscopy, proteomics, quantitative phosphoproteomics, biochemical analyses with extracts of the postsynaptic density (PSD), and an animal model of cerebral ischemia with mice overexpressing neuronal tPA to study whether the presynaptic release of tPA also has an effect on the postsynaptic terminal...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27881924/rodent-models-of-diabetic-nephropathy-their-utility-and-limitations
#15
REVIEW
Munehiro Kitada, Yoshio Ogura, Daisuke Koya
Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes...
2016: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/27881195/the-involvement-of-runx2-and-sparc-genes-in-the-bacterial-chondronecrosis-with-osteomyelitis-in-broilers
#16
E Paludo, A M G Ibelli, J O Peixoto, F C Tavernari, C A V Lima-Rosa, J R C Pandolfi, M C Ledur
Economic losses due to an increase of leg disorders in broilers have become a major concern of the poultry industry. Despite the efforts to reduce skeletal abnormalities in chickens, insufficient progress has been made. Bacterial chondronecrosis with osteomyelitis (BCO) is one of the main disorders that affect bone integrity in broilers. However, the genetic pathways and genes involved in most bone problems, including BCO, remains unclear. In this study, femoral samples from male broilers with 45 days of age affected or not with BCO were used to compare the relative expression with a reverse transcription real time PCR approach of 13 candidate genes: SPP1 (osteopontin), TNFRSF11B (osteoprotegerin), SPARC (osteonectin), CALB1 (calbidin 1), CALM (Calmodulin 2), IBSP (sialoprotein), COL1A2 (collagen, type I, α 2), BMP2 (bone morphogenetic protein 2), BMP3 (bone morphogenetic protein 3), RANKL (κ-B nuclear factor ligand), SMAD1 (SMAD family member 1), LEPR (leptin receptor) and RUNX2 (related transcription factor Runt 2)...
November 24, 2016: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/27878554/the-involvement-of-the-decrease-of-astrocytic-wnt5a-in-the-cognitive-decline-in-minimal-hepatic-encephalopathy
#17
Saidan Ding, Zhu Xu, Jianjing Yang, Leping Liu, Xueli Huang, Xuebao Wang, Qichuan Zhuge
Wnt signaling plays a key role in neuroprotection and synaptic plasticity. We speculate that the impairment of Wnt signaling may mediate astrocytic neurotrophins (NTs) production and the impairment of Wnt signaling to astrocytic NTs production contributes to the pathogenesis of minimal hepatic encephalopathy (MHE). Here, we found that induction of astrocytic NTs synthesis was by Wnt5a via the calcium/calmodulin-sensitive protein kinase II (CaMK II)-cAMP-response element-binding protein (CREB) pathway in PCAs...
November 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27876793/pep-19-modulates-calcium-binding-to-calmodulin-by-electrostatic-steering
#18
Xu Wang, John A Putkey
PEP-19 is a small protein that increases the rates of Ca(2+) binding to the C-domain of calmodulin (CaM) by an unknown mechanism. Although an IQ motif promotes binding to CaM, an acidic sequence in PEP-19 is required to modulate Ca(2+) binding and to sensitize HeLa cells to ATP-induced Ca(2+) release. Here, we report the NMR solution structure of a complex between PEP-19 and the C-domain of apo CaM. The acidic sequence of PEP-19 associates between helices E and F of CaM via hydrophobic interactions. This allows the acidic side chains in PEP-19 to extend toward the solvent and form a negatively charged surface that resembles a catcher's mitt near Ca(2+) binding loop III of CaM...
November 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/27875595/phosphorylation-of-serine-235-of-the-hepatitis-c-virus-non-structural-protein-ns5a-by-multiple-kinases
#19
Kuan-Ying Lee, Yi-Hung Chen, Shih-Chin Hsu, Ming-Jiun Yu
Phosphorylation at serine 235 (S235) of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) plays a critical role in the viral life cycle. For medical and virological interests, we exploited the HEK293T kidney cells to test 3 candidate protein kinases on NS5A S235 phosphorylation. Inhibitors that inhibit casein kinase I α (CKIα), polo-like kinase I (PlKI) or calmodulin-dependent kinase II (CaMKII) all reduced NS5A S235 phosphorylation. CKIα was studied previously and PlKI had severe cytotoxicity, thus CaMKII was selected for validation in the Huh7...
2016: PloS One
https://www.readbyqxmd.com/read/27875582/changes-in-intracellular-na-following-enhancement-of-late-na-current-in-virtual-human-ventricular-myocytes
#20
Karen Cardona, Beatriz Trenor, Wayne R Giles
The slowly inactivating or late Na+ current, INa-L, can contribute to the initiation of both atrial and ventricular rhythm disturbances in the human heart. However, the cellular and molecular mechanisms that underlie these pro-arrhythmic influences are not fully understood. At present, the major working hypothesis is that the Na+ influx corresponding to INa-L significantly increases intracellular Na+, [Na+]i; and the resulting reduction in the electrochemical driving force for Na+ reduces and (may reverse) Na+/Ca2+ exchange...
2016: PloS One
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