The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform
Alberto Ferrus - One of the best experts on this subject based on the ideXlab platform.
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Plasticity of motor nerve terminals in Drosophila T(X, Y) V7 mutant: Effect of deregulation of the novel calcium-binding protein frequenin
Neuroscience Letters, 1993Co-Authors: Denise Angaut-petit, Alberto Ferrus, Lucette FailleAbstract:Abstract The Drosophila T(X, Y) V7 mutant is characterized by abnormally large motor responses that build up upon repetitive stimulation. Genetically it is characterized by a chromosomal breakpoint located at the proximal end of the Shaker Gene complex. This mutation affects a Gene which encodes a novel calcium-binding protein: the frequenin. Since neuronal activity is known to affect neurite elongation we looked for the geometry of motor terminal arborization in this mutant. Our results show a significant reduction in number and length of motor terminal branches in mutants as compared to wild type. This observation is opposite to the effect of other hyperexcitable mutations such as Shaker or ether-a-gogo or Hyperkinetic . Thus the V7 phenotype cannot be interpreted as a result of changes in motoneuron firing pattern. According to results obtained on transformed larvae in which frequenin cDNA expression was under the control of a heat shock promoter, it appears that the morphological phenotype of V7 may be due to specific effects of deregulation of this calcium-binding protein.
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Nerve terminal excitability and neuromuscular transmission in T(X;Y)V7 and Shaker mutants of Drosophila melanogaster.
Journal of Neurogenetics, 1991Co-Authors: A. Mallart, D. Angaut-petit, C. Bourret-poulain, Alberto FerrusAbstract:We investigated the neuromuscular transmission in relation with Genetic neuronal excitability changes in mutants T(X;Y)V7 and ShKS133 of Drosophila. These mutations affect two different Genes belonging to the Shaker Gene complex which encode different yet functionally related proteins. Experiments were performed on neuromuscular junctions from Drosophila larvae by recording pre- and postsynatic membrane currents using external electrodes. It was found that the neuromuscular electrophysiological phenotype of T(X;Y)V7 is caused by presynaptic membrane hyperexcitability probably in relation with a Ca2+-dependent down regulation of voltage dependent K channels. By contrast, the ShKS133 phenotype can be explained solely by action potential widening due to the absence of type-A K channels.
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troponin i is encoded in the haplolethal region of the Shaker Gene complex of drosophila
Genes & Development, 1991Co-Authors: Julio A Barbas, Joan Galceran, I Krahjentgens, J L De La Pompa, Inmaculada Canal, Olaf Pongs, Alberto FerrusAbstract:: We have analyzed one of the nine complementation groups that constitute the haplolethal (HL) region of the Shaker Gene complex (ShC). Five mutations, including a dominant lethal, define this complementation group: HL I. Mutant phenotypes show abnormal embryoGenesis with structural defects in the nervous system and aberrant deGeneration of specific adult muscles in addition to altered action potentials. HL I encodes a family of proteins with extensive homology to invertebrate troponin I (TnI). Members of this family are brought about by two alternative and two mutually exclusive exons in conjunction with two differential polyadenylation sites. Transcription analysis indicates that some isoforms are adult specific and others are synthesized throughout development, except during early metamorphosis. Certain isoforms of Drosophila TnI are expressed in specific muscles. The specificity of mutant phenotypes suggests a functional role of particular TnI isoforms in the development and the mature activity of muscle and nervous systems.
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Genetic analysis of the Shaker Gene complex of drosophila melanogaster
Genetics, 1990Co-Authors: Alberto Ferrus, J L De La Pompa, S Llamazares, M A Tanouye, Olaf PongsAbstract:The Shaker complex (ShC) spans over 350 kb in the 16F region of the X chromosome. It can be dissected by means of aneuploids into three main sections: the maternal effect (ME), the viable (V) and the haplolethal (HL) regions. The mutational analysis of ShC shows a high density of antimorphic mutations among 12 lethal complementation groups in addition to 14 viable alleles. The complex is the structural locus of a family of potassium channels as well as a number of functions relevant to the biology of the nervous system. The constituents of ShC seem to be linked by functional relationships in view of the similarity of the phenotypes, antimorphic nature of their mutations and the behavior in transheterozygotes. We discuss the relationship between the Genetic organization of ShC and the functional coupling of potassium currents with the other functions encoded in the complex.
Lawrence Salkoff - One of the best experts on this subject based on the ideXlab platform.
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The major delayed rectifier in both Drosophila neurons and muscle is encoded by Shab
The Journal of Neuroscience, 1995Co-Authors: S Tsunoda, Lawrence SalkoffAbstract:The delayed rectifier K+ current in Drosophila is similar to the classical delayed rectifier, originally described by Hodgkin and Huxley. Drosophila provides unique tools of mutant analysis to unambiguously determine the Genetic identity of this native K+ current. We identified the Shab Gene as the exclusive Gene underlying delayed rectifier currents in both muscle and neurons. In muscles, a Genetic mutation of Shab removes virtually all the whole cell delayed rectifier current (IK), while leaving unaltered the transient A-current encoded by the Shaker Gene. In neurons, the Shab mutation also removes the bulk of IK, but leaves unaltered the transient A-current encoded by the Shal Gene. Although most of the delayed rectifier current is the product of the Shab Gene, the Shaw Gene contributes a small “leak” current to most neurons and muscle cells. Thus, in contrast to the A-currents which are encoded by different Genes in muscle and neuronal cell bodies (Shaker and Shal, respectively), the predominant IK in both muscle and neurons is encoded by the same Gene (Shab). With the Genetic identity of IK confirmed, all of the major K+ currents in embryonic Drosophila neurons and muscle are now known.
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Shaker, Shal, Shab, and Shaw express independent K^+ current systems
Neuron, 1991Co-Authors: Manuel Covarrubias, Lawrence SalkoffAbstract:Although many K+ channel Genes encoding homologous subunits have been cloned, a central question remains: how do these subunits associate to produce the diversity of K+ currents observed in living cells? Previous work has shown that different subunits encoded by the Shaker Gene subfamily are able to form heteromultimers, which add to the diversity of currents. However, the unrestrained mixing of subunits from all Genes to form hybrid channels would be undesirable for some cells that clearly require functionally discrete K+ currents. We show that Drosophila Shaker, Shal, Shab, and Shaw subunits form functional homomultimers, but that a molecular barrier to heteropolymerization is present. Coexpression of all four K+ channel systems does not alter their individual properties in any way. These experiments also demonstrate that multiple, independent A-current systems together with multiple, independent delayed rectifier systems can coexist in single cells.
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K+ current diversity is produced by an extended Gene family conserved in Drosophila and mouse.
Science, 1990Co-Authors: Manuel Covarrubias, Keith Baker, Alice Butler, Lawrence SalkoffAbstract:The Drosophila Shaker Gene on the X chromosome has three sister Genes, Shal, Shab, and Shaw, which map to the second and third chromosomes. This extended Gene family encodes voltage-gated potassium channels with widely varying kinetics (rate of macroscopic current activation and inactivation) and voltage sensitivity of steady-state inactivation. The differences in the currents of the various Gene products are greater than the differences produced by alternative splicing of the Shaker Gene. In Drosophila, the transient (A current) subtype of the potassium channel (Shaker and Shal) and the delayed-rectifier subtype (Shab and Shaw) are encoded by homologous Genes, and there is more than one Gene for each subtype of channel. Homologs of Shaker, Shal, Shab, and Shaw are present in mammals; each Drosophila potassium-channel Gene may be represented as a multiGene subfamily in mammals.
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the drosophila Shaker Gene codes for a distinctive k current in a subset of neurons
Neuron, 1990Co-Authors: Keith Baker, Lawrence SalkoffAbstract:Abstract A transient K + current coded by the Shaker Gene was identified in muscle and expressed in Xenopus oocytes by injecting cRNA transcribed from a cloned cDNA. The Shaker current has not previously been identified in neurons. Mutational analysis now reveals that in neurons, Shaker is required for expression of a very rapidly inactivating K + current with a depolarized steady-state inactivation curve. Together, these properties distinguish the Shaker -coded current from similar fast transient K + currents coded by other Genes. The Sh 5 mutation further enhanced the depolarization of the Shaker current steady-state inactivation curve. Deletion of the Shaker Gene completely removes the transient K + current from a small percentage of neurons (15%) in a mixed population, and removes a portion of the whole-cell current in about 35% of neurons. The remaining 50% of neurons were apparently unaffected by deletion of the Shaker Gene. The unique combination of rapid inactivation and depolarized steady-state inactivation of the Shaker current may reflect a unique functional role for this curent in the nervous system such as the rapid repolarization of action potentials.
Olaf Pongs - One of the best experts on this subject based on the ideXlab platform.
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Novel potassium channels encoded by the Shaker locus in drosophila photoreceptors
Neuron, 1991Co-Authors: Roger C. Hardie, Olaf Pongs, Dieter Voss, Simon B. LaughlinAbstract:Abstract The Shaker Gene, responsible for A-type potassium channels in Drosophila muscle, encodes a large family of transcripts capable of Generating a variety of kinetically distinct A channels when expressed in oocytes. We describe a distinct class of A channel encoded by the Shaker Gene in a novel preparation of dissociated Drosophila photoreceptors. Whole-cell recordings reveal a rapidly inactivating A current that is absent in Shaker mutants and that can be readily isolated in cell-attached patches. Although very similar to their muscle counterparts, the photoreceptor A channels show a striking 40–50 mV negative shift in their voltage-operating range. Two mutations ( Sh E62 and T(1;Y)W32 ), which exclude only certain classes of Shaker transcripts, were used to show that photoreceptor A channels are encoded by multiple transcripts distinct from those encoding muscle A channels, while PCR techniques identified four transcripts ( Sh Al, Sh A2, Sh G1, and Sh G2) in mRNA from dissected retina.
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troponin i is encoded in the haplolethal region of the Shaker Gene complex of drosophila
Genes & Development, 1991Co-Authors: Julio A Barbas, Joan Galceran, I Krahjentgens, J L De La Pompa, Inmaculada Canal, Olaf Pongs, Alberto FerrusAbstract:: We have analyzed one of the nine complementation groups that constitute the haplolethal (HL) region of the Shaker Gene complex (ShC). Five mutations, including a dominant lethal, define this complementation group: HL I. Mutant phenotypes show abnormal embryoGenesis with structural defects in the nervous system and aberrant deGeneration of specific adult muscles in addition to altered action potentials. HL I encodes a family of proteins with extensive homology to invertebrate troponin I (TnI). Members of this family are brought about by two alternative and two mutually exclusive exons in conjunction with two differential polyadenylation sites. Transcription analysis indicates that some isoforms are adult specific and others are synthesized throughout development, except during early metamorphosis. Certain isoforms of Drosophila TnI are expressed in specific muscles. The specificity of mutant phenotypes suggests a functional role of particular TnI isoforms in the development and the mature activity of muscle and nervous systems.
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Genetic analysis of the Shaker Gene complex of drosophila melanogaster
Genetics, 1990Co-Authors: Alberto Ferrus, J L De La Pompa, S Llamazares, M A Tanouye, Olaf PongsAbstract:The Shaker complex (ShC) spans over 350 kb in the 16F region of the X chromosome. It can be dissected by means of aneuploids into three main sections: the maternal effect (ME), the viable (V) and the haplolethal (HL) regions. The mutational analysis of ShC shows a high density of antimorphic mutations among 12 lethal complementation groups in addition to 14 viable alleles. The complex is the structural locus of a family of potassium channels as well as a number of functions relevant to the biology of the nervous system. The constituents of ShC seem to be linked by functional relationships in view of the similarity of the phenotypes, antimorphic nature of their mutations and the behavior in transheterozygotes. We discuss the relationship between the Genetic organization of ShC and the functional coupling of potassium currents with the other functions encoded in the complex.
J L De La Pompa - One of the best experts on this subject based on the ideXlab platform.
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troponin i is encoded in the haplolethal region of the Shaker Gene complex of drosophila
Genes & Development, 1991Co-Authors: Julio A Barbas, Joan Galceran, I Krahjentgens, J L De La Pompa, Inmaculada Canal, Olaf Pongs, Alberto FerrusAbstract:: We have analyzed one of the nine complementation groups that constitute the haplolethal (HL) region of the Shaker Gene complex (ShC). Five mutations, including a dominant lethal, define this complementation group: HL I. Mutant phenotypes show abnormal embryoGenesis with structural defects in the nervous system and aberrant deGeneration of specific adult muscles in addition to altered action potentials. HL I encodes a family of proteins with extensive homology to invertebrate troponin I (TnI). Members of this family are brought about by two alternative and two mutually exclusive exons in conjunction with two differential polyadenylation sites. Transcription analysis indicates that some isoforms are adult specific and others are synthesized throughout development, except during early metamorphosis. Certain isoforms of Drosophila TnI are expressed in specific muscles. The specificity of mutant phenotypes suggests a functional role of particular TnI isoforms in the development and the mature activity of muscle and nervous systems.
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Genetic analysis of the Shaker Gene complex of drosophila melanogaster
Genetics, 1990Co-Authors: Alberto Ferrus, J L De La Pompa, S Llamazares, M A Tanouye, Olaf PongsAbstract:The Shaker complex (ShC) spans over 350 kb in the 16F region of the X chromosome. It can be dissected by means of aneuploids into three main sections: the maternal effect (ME), the viable (V) and the haplolethal (HL) regions. The mutational analysis of ShC shows a high density of antimorphic mutations among 12 lethal complementation groups in addition to 14 viable alleles. The complex is the structural locus of a family of potassium channels as well as a number of functions relevant to the biology of the nervous system. The constituents of ShC seem to be linked by functional relationships in view of the similarity of the phenotypes, antimorphic nature of their mutations and the behavior in transheterozygotes. We discuss the relationship between the Genetic organization of ShC and the functional coupling of potassium currents with the other functions encoded in the complex.
B Rudy - One of the best experts on this subject based on the ideXlab platform.
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Differential expression of Shaw-related K+ channels in the rat central nervous system.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1994Co-Authors: M Weiser, E Vega-saenz De Miera, C Kentros, H Moreno, L Franzen, D Hillman, H Baker, B RudyAbstract:The family of mammalian Genes related to the Drosophila Shaker Gene, consisting of four subfamilies, is thought to encode subunits of tetrameric voltage-gated K+ channels. There is compelling evidence that subunits of the same subfamily, but not of different subfamilies, form heteromultimeric channels in vitro, and thus, each Gene subfamily is postulated to encode components of an independent channel system. In order to identify cells with native channels containing subunits of one of these subfamilies (Shaw-related or ShIII), the cellular distribution of ShIII transcripts was examined by Northern blot analysis and in situ hybridization. Three of four ShIII Genes (KV3.1, KV3.2, and KV3.3) are expressed mainly in the CNS. KV3.4 transcripts are also present in the CNS but are more abundant in skeletal muscle. In situ hybridization studies in the CNS reveal discrete and specific neuronal populations that prominently express ShIII mRNAs, both in projecting and in local circuit neurons. In the cerebral cortex, hippocampus, and caudate-putamen, subsets of neurons can be distinguished by the expression of specific ShIII mRNAs. Each ShIII Gene exhibits a unique pattern of expression; however, many neuronal populations expressing KV3.1 transcripts also express KV3.3 mRNAs. Furthermore, KV3.4 transcripts are present, albeit at lower levels, in several of the neuronal populations that also express KV3.1 and/or KV3.3 mRNAs, revealing a high potential for heteromultimer formation between the products of three of the four Genes. Expression of ShIII cRNAs in Xenopus oocytes was used to explore the functional consequences of heteromultimer formation between ShIII subunits. Small amounts of KV3.4 cRNA, which expresses small, fast-inactivating currents when injected alone, produced fast-inactivating currents that are severalfold larger when coinjected with an excess of KV3.1 or KV3.3 cRNA. This amplification is due to both an increase in single-channel conductance in the heteromultimeric channels and the observation that less than four, perhaps even a single KV3.4 subunit is sufficient to impart fast-inactivating properties to the channel. The oocyte experiments indicate that the apparently limited, low-level expression of KV3.4 in the CNS is potentially significant. The anatomical studies suggest that heteromultimer formation between ShIII proteins might be a common feature in the CNS. Moreover, the possibility that the subunit composition of heteromultimers varies in different neurons should be considered, since the ratios of overlapping signals change from one neuronal population to another. In order to proceed with functional analysis of native ShIII channels, it is important to known which subunit compositions might occur in vivo. The studies presented here provide important clues for the identification of native homo- and heteromultimeric ShIII channels in neurons.
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the role of the divergent amino and carboxyl domains on the inactivation properties of potassium channels derived from the Shaker Gene of drosophila
The Journal of Neuroscience, 1990Co-Authors: L E Iverson, B RudyAbstract:Several products Generated from the Drosophila Shaker Gene by alternative splicing predict a group of similar proteins with an identical central and variable amino and carboxyl domains. We have constructed 9 Sh cDNAs combining 3 different 5′ domains with 3 different 3′ domains. RNA transcribed from 6 of these cDNAs induce K+ currents in Xenopus oocytes. All currents share similar properties of voltage dependence, potassium selectivity, and block by 4-AP, TEA, and charybdotoxin. These properties presumably result from a channel core formed by the identical central region of the proteins. The currents differ in macroscopic inactivation kinetics. Five RNAs induced K+ currents which inactivate, each at distinct rates, during short depolarizations. The sixth RNA induces a current that essentially does not inactivate unless depolarized for many seconds. This raises the possibility that Sh may encode nontransient as well as transient K+ currents. Analysis of currents produced by the various combinations suggests that the divergent amino domains influence the stability of a first, nonabsorbing, inactivated state. This results in striking differences in the probability of channel reopening, as observed in single-channel recordings, of those channels with identical carboxyl but different amino domains. Furthermore, based on macroscopic analysis of the currents, we suggest that the primary role of the carboxyl domains is to influence the relative stability between the first and a second inactivated state. The second inactivated state is essentially absorbing, and recovery from this state is very slow. The observed differences in the rates of recovery from inactivation of channels containing different carboxyl domains reflect differences in the rates at which they enter this second inactivated state.