The Experts below are selected from a list of 15 Experts worldwide ranked by ideXlab platform
Ralf Stanewsky - One of the best experts on this subject based on the ideXlab platform.
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Function of the Shaw Potassium Channel within the Drosophila Circadian Clock
2013Co-Authors: James J L Hodge, Ralf StanewskyAbstract:Background: In addition to the molecular feedback loops, electrical activity has been shown to be important for the function of networks of clock neurons in generating rhythmic behavior. Most studies have used over-expression of foreign Channels or pharmacological manipulations that alter membrane excitability. In order to determine the cellular mechanisms that regulate resting membrane potential (RMP) in the native clock of Drosophila we modulated the function of Shaw, a widely expressed neuronal Potassium (K +) Channel known to regulate RMP in Drosophila central neurons. Methodology/Principal Findings: We show that Shaw is endogenously expressed in clock neurons. Differential use of clock gene promoters was employed to express a range of transgenes that either increase or decrease Shaw function in different clusters of clock neurons. Under LD conditions, increasing Shaw levels in all clock neurons (LNv, LNd, DN1, DN2 and DN3), or in subsets of clock neurons (LNd and DNs or DNs alone) increases locomotor activity at night. In free-running conditions these manipulations result in arrhythmic locomotor activity without disruption of the molecular clock. Reducing Shaw in the DN alone caused a dramatic lengthening of the behavioral period. Changing Shaw levels in all clock neurons also disrupts the rhythmic accumulation and levels of Pigment Dispersing Factor (PDF) in the dorsal projections of LNv neurons. However, changing Shaw levels solely in LNv neurons had little effect on locomotor activity or rhythmic accumulation of PDF
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Function of the Shaw Potassium Channel within the Drosophila circadian clock.
PloS one, 2008Co-Authors: James J L Hodge, Ralf StanewskyAbstract:Background In addition to the molecular feedback loops, electrical activity has been shown to be important for the function of networks of clock neurons in generating rhythmic behavior. Most studies have used over-expression of foreign Channels or pharmacological manipulations that alter membrane excitability. In order to determine the cellular mechanisms that regulate resting membrane potential (RMP) in the native clock of Drosophila we modulated the function of Shaw, a widely expressed neuronal Potassium (K+) Channel known to regulate RMP in Drosophila central neurons. Methodology/Principal Findings We show that Shaw is endogenously expressed in clock neurons. Differential use of clock gene promoters was employed to express a range of transgenes that either increase or decrease Shaw function in different clusters of clock neurons. Under LD conditions, increasing Shaw levels in all clock neurons (LNv, LNd, DN1, DN2 and DN3), or in subsets of clock neurons (LNd and DNs or DNs alone) increases locomotor activity at night. In free-running conditions these manipulations result in arrhythmic locomotor activity without disruption of the molecular clock. Reducing Shaw in the DN alone caused a dramatic lengthening of the behavioral period. Changing Shaw levels in all clock neurons also disrupts the rhythmic accumulation and levels of Pigment Dispersing Factor (PDF) in the dorsal projections of LNv neurons. However, changing Shaw levels solely in LNv neurons had little effect on locomotor activity or rhythmic accumulation of PDF. Conclusions/Significance Based on our results it is likely that Shaw modulates pacemaker and output neuronal electrical activity that controls circadian locomotor behavior by affecting rhythmic release of PDF. The results support an important role of the DN clock neurons in Shaw-mediated control of circadian behavior. In conclusion, we have demonstrated a central role of Shaw for coordinated and rhythmic output from clock neurons.
James J L Hodge - One of the best experts on this subject based on the ideXlab platform.
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Function of the Shaw Potassium Channel within the Drosophila Circadian Clock
2013Co-Authors: James J L Hodge, Ralf StanewskyAbstract:Background: In addition to the molecular feedback loops, electrical activity has been shown to be important for the function of networks of clock neurons in generating rhythmic behavior. Most studies have used over-expression of foreign Channels or pharmacological manipulations that alter membrane excitability. In order to determine the cellular mechanisms that regulate resting membrane potential (RMP) in the native clock of Drosophila we modulated the function of Shaw, a widely expressed neuronal Potassium (K +) Channel known to regulate RMP in Drosophila central neurons. Methodology/Principal Findings: We show that Shaw is endogenously expressed in clock neurons. Differential use of clock gene promoters was employed to express a range of transgenes that either increase or decrease Shaw function in different clusters of clock neurons. Under LD conditions, increasing Shaw levels in all clock neurons (LNv, LNd, DN1, DN2 and DN3), or in subsets of clock neurons (LNd and DNs or DNs alone) increases locomotor activity at night. In free-running conditions these manipulations result in arrhythmic locomotor activity without disruption of the molecular clock. Reducing Shaw in the DN alone caused a dramatic lengthening of the behavioral period. Changing Shaw levels in all clock neurons also disrupts the rhythmic accumulation and levels of Pigment Dispersing Factor (PDF) in the dorsal projections of LNv neurons. However, changing Shaw levels solely in LNv neurons had little effect on locomotor activity or rhythmic accumulation of PDF
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Function of the Shaw Potassium Channel within the Drosophila circadian clock.
PloS one, 2008Co-Authors: James J L Hodge, Ralf StanewskyAbstract:Background In addition to the molecular feedback loops, electrical activity has been shown to be important for the function of networks of clock neurons in generating rhythmic behavior. Most studies have used over-expression of foreign Channels or pharmacological manipulations that alter membrane excitability. In order to determine the cellular mechanisms that regulate resting membrane potential (RMP) in the native clock of Drosophila we modulated the function of Shaw, a widely expressed neuronal Potassium (K+) Channel known to regulate RMP in Drosophila central neurons. Methodology/Principal Findings We show that Shaw is endogenously expressed in clock neurons. Differential use of clock gene promoters was employed to express a range of transgenes that either increase or decrease Shaw function in different clusters of clock neurons. Under LD conditions, increasing Shaw levels in all clock neurons (LNv, LNd, DN1, DN2 and DN3), or in subsets of clock neurons (LNd and DNs or DNs alone) increases locomotor activity at night. In free-running conditions these manipulations result in arrhythmic locomotor activity without disruption of the molecular clock. Reducing Shaw in the DN alone caused a dramatic lengthening of the behavioral period. Changing Shaw levels in all clock neurons also disrupts the rhythmic accumulation and levels of Pigment Dispersing Factor (PDF) in the dorsal projections of LNv neurons. However, changing Shaw levels solely in LNv neurons had little effect on locomotor activity or rhythmic accumulation of PDF. Conclusions/Significance Based on our results it is likely that Shaw modulates pacemaker and output neuronal electrical activity that controls circadian locomotor behavior by affecting rhythmic release of PDF. The results support an important role of the DN clock neurons in Shaw-mediated control of circadian behavior. In conclusion, we have demonstrated a central role of Shaw for coordinated and rhythmic output from clock neurons.
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Shaw Potassium Channel genes in Drosophila.
Journal of neurobiology, 2005Co-Authors: James J L Hodge, James C. Choi, Cahir J. O'kane, Leslie C. GriffithAbstract:Drosophila Shaw encodes a voltage-insensitive, slowly activating, noninactivating K(+) current. The functional and developmental roles of this Channel are unknown. In this study, we use a dominant transgenic strategy to investigate Shaw function and describe a second member of the Shaw family, Shawl. In situ hybridization showed that the two Shaw family genes, Shaw and Shawl, have largely nonoverlapping expression patterns in embryos. Shaw is expressed mainly in excitable cells of the CNS and PNS of late embryos. Shawl is expressed in many nonexcitable cell types: ubiquitously in embryos until the germband extends, then transiently in the developing CNS and PNS, becoming restricted to progressively smaller subsets of the CNS. Ectopic full-length and truncated Shaw localize differently within neurons, and produce uneclosed small pupae and adults with unfurled wings and softened cuticle. This phenotype was mapped to the crustacean cardioactive peptide (CCAP)-neuropeptide circuit. Widespread expression of Shaw in the nervous system results in a reduction in body mass, ether-induced shaking, and lethality. Expression of full-length Shaw had more extreme phenotypic consequences and caused earlier lethality than expression of truncated Shaw in a given GAL4 pattern. Whole cell recordings from ventral ganglion motor neurons expressing the truncated Shaw protein suggest that a major role of Shaw Channels in these cells is to contribute to the resting potential.
Francesc Graus - One of the best experts on this subject based on the ideXlab platform.
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Immunoproteomic studies on paediatric opsoclonus-myoclonus associated with neuroblastoma.
Journal of neuroimmunology, 2016Co-Authors: Estefanía Torres-vega, María Durán-moreno, Manuel M. Sánchez Del Pino, Yania Yáñez, Adela Cañete, Victoria Castel, Rogelio López-cuevas, Juan J. Vílchez, Josep Dalmau, Francesc GrausAbstract:We aimed to identify new cell-membrane antigens implicated in opsoclonus-myoclonus with neuroblastoma. The sera of 3 out of 14 patients showed IgG electron-microscopy immunogold reactivity on SH-SY5Y neuroblastoma cells. Immunoprecipitation experiments using rat brain synaptosomes and SH-SY5Y cells led to the identification of: (1) thirty-one nuclear/cytoplasmic proteins (including antigens HuB, HuC); (2) seven neuronal membrane proteins, including the Shaw-Potassium Channel Kv3.3 (KCNC3), whose genetic disruption in mice causes ataxia and generalized muscle twitching. Although cell-based assays did not demonstrate direct antigenicity, our findings point to Shaw-related subfamily of the Potassium voltage-gated Channels complexed proteins as hypothetical antigenic targets.
N Heintz - One of the best experts on this subject based on the ideXlab platform.
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Kv3.3b: a novel Shaw type Potassium Channel expressed in terminally differentiated cerebellar Purkinje cells and deep cerebellar nuclei
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1994Co-Authors: Ds Goldman-wohl, E Chan, D Baird, N HeintzAbstract:A two-step hybridization/subtraction procedure was employed to isolate markers for the later stages of Purkinje cell differentiation. From this screen, a novel Shaw Potassium Channel cDNA (Kv3.3b) was identified that is developmentally regulated. Expression of this Channel is highly enriched in the brain, particularly in the cerebellum, where its expression is confined to Purkinje cells and deep cerebellar nuclei. Sequence analysis revealed that it is an alternatively spliced form of the mouse Kv3.3 gene, and that the previously reported Kv3.3 mRNA (Ghanshani et al., 1992) is not expressed in cerebellum. Expression of the Kv3.3b mRNA begins in cerebellar Purkinje cells between postnatal day 8 (P8) and P10 and continues through adulthood, coinciding with elaboration of the mature Purkinje cell dendritic arbor. The timing of expression of Kv3.3b mRNA is maintained in mixed, dissociated primary cerebellar cell culture. These results suggest that the Kv3.3b K+ Channel function is restricted to terminally differentiated Purkinje cells, and that analysis of the mechanisms governing its expression in vivo and in vitro can reveal molecular mechanisms governing Purkinje cell differentiation.
Estefanía Torres-vega - One of the best experts on this subject based on the ideXlab platform.
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Immunoproteomic studies on paediatric opsoclonus-myoclonus associated with neuroblastoma.
Journal of neuroimmunology, 2016Co-Authors: Estefanía Torres-vega, María Durán-moreno, Manuel M. Sánchez Del Pino, Yania Yáñez, Adela Cañete, Victoria Castel, Rogelio López-cuevas, Juan J. Vílchez, Josep Dalmau, Francesc GrausAbstract:We aimed to identify new cell-membrane antigens implicated in opsoclonus-myoclonus with neuroblastoma. The sera of 3 out of 14 patients showed IgG electron-microscopy immunogold reactivity on SH-SY5Y neuroblastoma cells. Immunoprecipitation experiments using rat brain synaptosomes and SH-SY5Y cells led to the identification of: (1) thirty-one nuclear/cytoplasmic proteins (including antigens HuB, HuC); (2) seven neuronal membrane proteins, including the Shaw-Potassium Channel Kv3.3 (KCNC3), whose genetic disruption in mice causes ataxia and generalized muscle twitching. Although cell-based assays did not demonstrate direct antigenicity, our findings point to Shaw-related subfamily of the Potassium voltage-gated Channels complexed proteins as hypothetical antigenic targets.