Histones and basic polypeptides activate Ca2+/cation influx in various cell types.
Ontology highlight
ABSTRACT:
SUBMITTER: Gamberucci A
PROVIDER: S-EPMC1219397 | biostudies-other | 1998 Apr
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Migration of oligodendrocyte progenitor cells (OPCs) from proliferative zones to their final location in the brain is an essential step in nervous system development. Golli proteins, products of the myelin basic protein gene, can modulate voltage-gated Ca(2+) uptake in OPCs during process extension and retraction. Given the importance of process extension/retraction on movement, the consequences of golli expression on OPC migration were examined in vivo and in vitro using time-lapse imaging of isolated OPCs and acute brain slice preparations from golli KO and golli J37 overexpressing mice (JOE). The results indicated that golli stimulated migration, and this enhanced motility was associated with increases in the activity of voltage operated Ca(2+) channels (VOCCs). Activation of VOCCs by high K(+) resulted in a significant increase in the migration speed of JOE OPCs versus control cells and golli-mediated modulation of OPC migration disappeared in the presence of VOCC antagonists. During migration, OPCs generated Ca(2+) oscillations that were dependent on voltage-calcium influx and both the amplitude and frequency of these Ca(2+) transients correlated positively with the rate of cell movement under a variety of pharmacological treatments. The Ca(2+) transient amplitude and the rate of cell movement were significantly lower in KO cells and significantly higher in JOE cells suggesting that the presence of golli promotes OPC migration by increasing the size of voltage-mediated Ca(2+) oscillations. These data define a new molecule that regulates Ca(2+) homeostasis in OPCs, and are the first to demonstrate that voltage-gated Ca(2+) channels can regulate an OPC function, such as migration.
| S-EPMC2739626 | biostudies-literature
Project description:Transient receptor potential channels have recently been implicated in physiological functions in a urogenital system. In this study, we investigated the role of transient receptor potential vanilloid 4 (TRPV4) channels in a stretch sensing mechanism in mouse primary urothelial cell cultures. The selective TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD) evoked Ca(2+) influx in wild-type (WT) urothelial cells, but not in TRPV4-deficient (TRPV4KO) cells. We established a cell-stretch system to investigate stretch-evoked changes in intracellular Ca(2+) concentration and ATP release. Stretch stimulation evoked intracellular Ca(2+) increases in a stretch speed- and distance-dependent manner in WT and TRPV4KO cells. In TRPV4KO urothelial cells, however, the intracellular Ca(2+) increase in response to stretch stimulation was significantly attenuated compared with that in WT cells. Stretch-evoked Ca(2+) increases in WT urothelium were partially reduced in the presence of ruthenium red, a broad TRP channel blocker, whereas that in TRPV4KO cells did not show such reduction. Potent ATP release occurred following stretch stimulation or 4alpha-PDD administration in WT urothelial cells, which was dramatically suppressed in TRPV4KO cells. Stretch-dependent ATP release was almost completely eliminated in the presence of ruthenium red or in the absence of extracellular Ca(2+). These results suggest that TRPV4 senses distension of the bladder urothelium, which is converted to an ATP signal in the micturition reflex pathway during urine storage.
| S-EPMC2755849 | biostudies-other
Project description:Store-operated Ca(2+) entry (SOCE) is a ubiquitous signaling process in eukaryotic cells in which the endoplasmic reticulum (ER)-localized Ca(2+) sensor, STIM1, activates the plasma membrane-localized Ca(2+) release-activated Ca(2+) (CRAC) channel, Orai1, in response to emptying of ER Ca(2+) stores. In efforts to understand this activation mechanism, we recently identified an acidic coiled-coil region in the C-terminus of Orai1 that contributes to physical association between these two proteins, as measured by fluorescence resonance energy transfer, and is necessary for Ca(2+) influx, as measured by an intracellular Ca(2+) indicator. Here, we present evidence that a positively charged sequence of STIM1 in its CRAC channel activating domain, human residues 384-386, is necessary for activation of SOCE, most likely because this sequence interacts directly with the acidic coiled coil of Orai1 to gate Ca(2+) influx. We find that mutation to remove positive charges in these residues in STIM1 prevents its stimulated association with wild-type Orai1. However, association does occur between this mutant STIM1 and Orai1 that is mutated to remove negative charges in its C-terminal coiled coil, indicating that other structural features are sufficient for this interaction. Despite this physical association, we find that thapsigargin fails to activate SOCE following coexpression of mutant STIM1 with either wild type or mutant Orai1, implicating STIM1 residues 384-386 in transmission of the Ca(2+) gating signal to Orai1 following store depletion.
| S-EPMC3236085 | biostudies-literature
Project description:Ca(2+) signaling in nonexcitable cells is typically initiated by receptor-triggered production of inositol-1,4,5-trisphosphate and the release of Ca(2+) from intracellular stores. An elusive signaling process senses the Ca(2+) store depletion and triggers the opening of plasma membrane Ca(2+) channels. The resulting sustained Ca(2+) signals are required for many physiological responses, such as T cell activation and differentiation. Here, we monitored receptor-triggered Ca(2+) signals in cells transfected with siRNAs against 2,304 human signaling proteins, and we identified two proteins required for Ca(2+)-store-depletion-mediated Ca(2+) influx, STIM1 and STIM2. These proteins have a single transmembrane region with a putative Ca(2+) binding domain in the lumen of the endoplasmic reticulum. Ca(2+) store depletion led to a rapid translocation of STIM1 into puncta that accumulated near the plasma membrane. Introducing a point mutation in the STIM1 Ca(2+) binding domain resulted in prelocalization of the protein in puncta, and this mutant failed to respond to store depletion. Our study suggests that STIM proteins function as Ca(2+) store sensors in the signaling pathway connecting Ca(2+) store depletion to Ca(2+) influx.
| S-EPMC3186072 | biostudies-literature
Project description:Maintenance of neural circuit activity requires appropriate regulation of excitatory and inhibitory synaptic transmission. Recently, glia have emerged as key partners in the modulation of neuronal excitability; however, the mechanisms by which glia regulate neuronal signaling are still being elucidated. Here, we describe an analysis of how Ca2+ signals within Drosophila astrocyte-like glia regulate excitability in the nervous system. We find that Drosophila astrocytes exhibit robust Ca2+ oscillatory activity manifested by fast, recurrent microdomain Ca2+ fluctuations within processes that infiltrate the synaptic neuropil. Unlike the enhanced neuronal activity and behavioral seizures that were previously observed during manipulations that trigger Ca2+ influx into Drosophila cortex glia, we find that acute induction of astrocyte Ca2+ influx leads to a rapid onset of behavioral paralysis and a suppression of neuronal activity. We observe that Ca2+ influx triggers rapid endocytosis of the GABA transporter (GAT) from astrocyte plasma membranes, suggesting that increased synaptic GABA levels contribute to the neuronal silencing and paralysis. We identify Rab11 as a novel regulator of GAT trafficking that is required for this form of activity regulation. Suppression of Rab11 function strongly offsets the reduction of neuronal activity caused by acute astrocyte Ca2+ influx, likely by inhibiting GAT endocytosis. Our data provide new insights into astrocyte Ca2+ signaling and indicate that distinct glial subtypes in the Drosophila brain can mediate opposing effects on neuronal excitability.
| S-EPMC5348542 | biostudies-literature
Project description:We performed the GeneChip analysis to identify multiple extracellular determinants such as cytokines, cell membrane-bound molecules, and matrix responsible for cardiomyogenic differentiation, and evaluated the statistical significance of differential gene expression by the NIA array analysis (http://lgsun.grc.nia.nih.gov/ANOVA/) (Bioinformatics 21: 2548), a web-based tool for microarrays data analysis. Keywords: Grem1-induced cardiogenesis via Wnt
2007-07-17 | GSE8481 | GEO
Project description:The NALP3 inflammasome is activated by low intracellular potassium concentrations [K(+)](i), leading to the secretion of the proinflammatory cytokine IL-1β. However, the mechanism of [K(+)](i) lowering after phagocytosis of monosodium urate crystals is still elusive. Here, we propose that endosomes containing monosodium urate crystals fuse with acidic lysosomes. The low pH in the phagolysosome causes a massive release of sodium and raises the intracellular osmolarity. This process is balanced by passive water influx through aquaporins leading to cell swelling. This process dilutes [K(+)](i) to values below the threshold of 90 mm known to activate NALP3 inflammasomes without net loss of cytoplasmic potassium ions. In vitro, the inhibitors of lysosomal acidification (ammonium chloride, chloroquine) and of aquaporins (mercury chloride, phloretin) all significantly decreased the production of IL-1β. In vivo, only the pharmacological inhibitor of lysosome acidification chloroquine could be used which again significantly reduced the IL-1β production. As a translational aspect one may consider the use of chloroquine for the anti-inflammatory treatment of refractory gout.
| S-EPMC3012992 | biostudies-literature
Project description:Cochlear inner hair cells (IHCs) develop from pre-sensory pacemaker to sound transducer. Here, we report that this involves changes in structure and function of the ribbon synapses between IHCs and spiral ganglion neurons (SGNs) around hearing onset in mice. As synapses matured they changed from holding several small presynaptic active zones (AZs) and apposed postsynaptic densities (PSDs) to one large AZ/PSD complex per SGN bouton. After the onset of hearing (i) IHCs had fewer and larger ribbons; (ii) CaV1.3 channels formed stripe-like clusters rather than the smaller and round clusters at immature AZs; (iii) extrasynaptic CaV1.3-channels were selectively reduced, (iv) the intrinsic Ca(2)(+) dependence of fast exocytosis probed by Ca(2)(+) uncaging remained unchanged but (v) the apparent Ca(2)(+) dependence of exocytosis linearized, when assessed by progressive dihydropyridine block of Ca(2)(+) influx. Biophysical modeling of exocytosis at mature and immature AZ topographies suggests that Ca(2)(+) influx through an individual channel dominates the [Ca(2)(+)] driving exocytosis at each mature release site. We conclude that IHC synapses undergo major developmental refinements, resulting in tighter spatial coupling between Ca(2)(+) influx and exocytosis.
| S-EPMC3989618 | biostudies-literature
Project description:The protein-mediated bidirectional electron transfer (ET) is the foundation of protein molecular wire, and plays an important role in the rapid detection of oxo-guanine-adenine DNA mismatches by MutY glycosylase. However, the influences of structural transitions on bidirectional ET are still not clear. In this work, the modified through-bond coupling (MTBC) model was further refined to correlate the structural transition and ET rate more quantitatively. With this model, various polyglycine structures (310-helix, ?-helix, ?-sheets, linear, polyproline helical I and II) were studied to explore the influences of structural transitions on bidirectional ET. It was found that the HOMO-LUMO gaps (?E) in CN (from the carboxyl to amino terminus) direction are much lower than that in opposite direction, except for polypro I. However, with the equal tunneling energy, the differences between bidirectional ET rates are slight for all structures. In structural transitions, we found that the ET rates are not only affected by the Ramachandran angles, but also correlated to the alignment of C?=?O vectors, the alignment of peptide planes and the rearrangement of other structure factors. The detailed information can be used to rationalize the inhomogeneous ET across different protein structures and design more efficient protein molecular wires.
| S-EPMC5703997 | biostudies-literature
Project description:The nonspecific divalent cation channel TRPM7 (transient receptor potential-melastatin-like 7) is involved in many Ca2+ and Mg2+-dependent cellular processes, including survival, proliferation and migration. TRPM7 expression predicts metastasis and recurrence in breast cancer and several other cancers. In cultured cells, it can induce an invasive phenotype by promoting Ca2+-mediated epithelial-mesenchymal transition. We previously showed that in neuroblastoma cells that overexpress TRPM7 moderately, stimulation with Ca2+-mobilizing agonists leads to a characteristic sustained influx of Ca2+. Here we report that sustained influx through TRPM7 is abruptly abrogated by elevating intracellular levels of cyclic adenosine monophosphate (cAMP). Using pharmacological inhibitors and overexpression studies we show that this blockage is mediated by the cAMP effector Protein Kinase A (PKA). Mutational analysis demonstrates that the Serine residue S1269, which is present proximal to the coiled-coil domain within the protein c-terminus, is responsible for sensitivity to cAMP.
| S-EPMC6322742 | biostudies-literature