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para  -  paralytic

Drosophila melanogaster

Synonyms: CG9907, DmNa[[V]], DmNa[[v]], DmNa[[v]]1, DmNav1, ...
 
 
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Disease relevance of para

  • When compared to wild type flies the toxicity of AaIT is greatly altered in knockdown resistant fly strains which are mutated in their para gene encoding the voltage gated sodium channel [1].
  • It is shown that embryos of ts paralytic alleles also show mild neural hypertrophy at permissive temperatures while short exposure to heat induces severe cuticle loss in these embryos. stmA exerts a maternal influence over heat-induced cuticle loss [2].
 

Psychiatry related information on para

  • Involvement of genes encoding a K+ channel (ether a go-go) and a Na+ channel (smellblind) in Drosophila olfaction [3].
 

High impact information on para

  • Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function [4].
  • We have characterized easily shocked (eas), a Drosophila "band-sensitive" paralytic mutant [5].
  • To identify the protein encoded by this gene and to elucidate the molecular basis of the mutant phenotypes, genomic DNA from the para locus was cloned [6].
  • Furthermore, the para transcript appears to undergo alternative splicing to produce several distinct subtypes of this channel [6].
  • Analysis of cDNAs revealed that the para locus comprises a minimum of 26 exons distributed over more than 60 kb of genomic DNA [6].
 

Biological context of para

  • Polymorphism data on para and elav (located at the middle region of the X chromosome) suggest that there is no population structure other than that caused by the X/4 fusion itself [7].
  • Polymorphism patterns at the paralytic (para) gene, located at the base of the X chromosome, suggest that there is suppressed crossing over in this region between fusion and nonfusion chromosomes but not within fusion and nonfusion chromosomes [7].
  • Mutations in the para gene encoding the subunit of the voltage-gated sodium channel also result in a similar phenotype [8].
  • Mutation of the axonal transport motor kinesin enhances paralytic and suppresses Shaker in Drosophila [9].
  • Here, we show that para transcripts undergo adenosine-to-inosine (A-to-I) RNA editing via a mechanism that apparently requires dsRNA secondary structure formation encompassing the edited exon and the downstream intron [10].
 

Anatomical context of para

  • Sh was additionally expressed in the photoreceptor cells of the retina and pupal flight muscle, while para and DSC were not [11].
  • In the pupal and adult, PNS expression of these genes is still distinct because only para transcripts are detected in wing sensory neurons [12].
  • The Drosophila para sodium channel alpha subunit was expressed in Xenopus oocytes alone and in combination with tipE, a putative Drosophila sodium channel accessory subunit [13].
  • Our previous work with temperature-sensitive (TS) paralytic alleles of comt has revealed a function for dNSF1 at synapses, where it appears to prime synaptic vesicles for neurotransmitter release [14].
  • We found that the BSC1 transcript was present in a wide range of tissues, including nerve cord, muscle, gut, fat body and ovary, whereas the para transcript was detected only in nerve cord and muscle [15].
 

Associations of para with chemical compounds

  • Point mutations in the Drosophila sodium channel gene para associated with resistance to DDT and pyrethroid insecticides [16].
  • We used an existing collection of Drosophila para mutants to examine the molecular basis of targetsite resistance to pyrethroids and DDT [16].
  • We expressed Drosophila para Na channels with and without these mutations and characterized their modification by deltamethrin [17].
  • We analyzed the consequences of V421M and L1029H mutations constructed in the Drosophila para sodium channel heterologously expressed in Xenopus oocytes, and found that both mutations confer channel insensitivity to permethrin, with the L1029H mutation having a more pronounced effect [18].
  • Previously we reported a mutation associated with pyrethroid resistance, Leu1029 to His, in domain II transmembrane segment S6 (IIS6) of the Heliothis virescens F. sodium channel (para homologue) hscp locus [19].
 

Physical interactions of para

  • Genetic-interaction studies with para demonstrate that blocking evoked fusion delays the accumulation of assembled SNARE complexes and behavioral paralysis that normally occurs in comatose mutants, indicating NSF activity is not required in the absence of vesicle fusion [20].
 

Regulatory relationships of para

 

Other interactions of para

  • The dsc1 gene encodes an ion channel of unknown function homologous to the paralytic (para) sodium channel, which mediates neuronal excitability [22].
  • A new temperature-sensitive paralytic mutant of Drosophila, comatose, is compared behaviorally and physiologically with the previously known types, para and shi [23].
  • When combined with para or mle mutations, Khe mutations cause synthetic lethality and a synergistic enhancement of TS-paralysis [9].
  • Neither eag (0.66), para (0.48), nor slo (0.63) differed significantly from the wild type [24].
  • Anesthetic sensitivity was also examined in mutant strains of D.m. which express abnormalities either in other potassium channel conductances (eag, slo) or other ion conductances (para) [24].
 

Analytical, diagnostic and therapeutic context of para

References

  1. The pharmacological flexibility of the insect voltage gated sodium channel: toxicity of AaIT to knockdown resistant (kdr) flies. Zlotkin, E., Devonshire, A.L., Warmke, J.W. Insect Biochem. Mol. Biol. (1999) [Pubmed]
  2. Effects of mutations at the stambh A locus of Drosophila melanogaster. Kumar, M., Joseph, M., Chandrashekaran, S. J. Genet. (2001) [Pubmed]
  3. Involvement of genes encoding a K+ channel (ether a go-go) and a Na+ channel (smellblind) in Drosophila olfaction. Dubin, A.E., Liles, M.M., Seligman, F., Le, T., Tolli, J., Harris, G.L. Ann. N. Y. Acad. Sci. (1998) [Pubmed]
  4. Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function. Feng, G., Deák, P., Chopra, M., Hall, L.M. Cell (1995) [Pubmed]
  5. The Drosophila easily shocked gene: a mutation in a phospholipid synthetic pathway causes seizure, neuronal failure, and paralysis. Pavlidis, P., Ramaswami, M., Tanouye, M.A. Cell (1994) [Pubmed]
  6. Molecular analysis of the para locus, a sodium channel gene in Drosophila. Loughney, K., Kreber, R., Ganetzky, B. Cell (1989) [Pubmed]
  7. Inferences on the evolutionary history of the Drosophila americana polymorphic X/4 fusion from patterns of polymorphism at the X-linked paralytic and elav genes. Vieira, C.P., Coelho, P.A., Vieira, J. Genetics (2003) [Pubmed]
  8. Phenotypic interaction between temperature-sensitive paralytic mutants comatose and paralytic suggests a role for N-ethylmaleimide-sensitive fusion factor in synaptic vesicle cycling in Drosophila. Sanyal, S., Basole, A., Krishnan, K.S. J. Neurosci. (1999) [Pubmed]
  9. Mutation of the axonal transport motor kinesin enhances paralytic and suppresses Shaker in Drosophila. Hurd, D.D., Stern, M., Saxton, W.M. Genetics (1996) [Pubmed]
  10. The mle(napts) RNA helicase mutation in drosophila results in a splicing catastrophe of the para Na+ channel transcript in a region of RNA editing. Reenan, R.A., Hanrahan, C.J., Barry, G. Neuron (2000) [Pubmed]
  11. Expression of ion channel genes in Drosophila. Tseng-Crank, J., Pollock, J.A., Hayashi, I., Tanouye, M.A. J. Neurogenet. (1991) [Pubmed]
  12. Spatial and temporal expression patterns of two sodium channel genes in Drosophila. Hong, C.S., Ganetzky, B. J. Neurosci. (1994) [Pubmed]
  13. Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology. Warmke, J.W., Reenan, R.A., Wang, P., Qian, S., Arena, J.P., Wang, J., Wunderler, D., Liu, K., Kaczorowski, G.J., Van der Ploeg, L.H., Ganetzky, B., Cohen, C.J. J. Gen. Physiol. (1997) [Pubmed]
  14. Genetic modifiers of the Drosophila NSF mutant, comatose, include a temperature-sensitive paralytic allele of the calcium channel alpha1-subunit gene, cacophony. Dellinger, B., Felling, R., Ordway, R.W. Genetics (2000) [Pubmed]
  15. Alternative splicing of the BSC1 gene generates tissue-specific isoforms in the German cockroach. Liu, Z., Chung, I., Dong, K. Insect Biochem. Mol. Biol. (2001) [Pubmed]
  16. Point mutations in the Drosophila sodium channel gene para associated with resistance to DDT and pyrethroid insecticides. Pittendrigh, B., Reenan, R., ffrench-Constant, R.H., Ganetzky, B. Mol. Gen. Genet. (1997) [Pubmed]
  17. Activation of Drosophila sodium channels promotes modification by deltamethrin. Reductions in affinity caused by knock-down resistance mutations. Vais, H., Williamson, M.S., Goodson, S.J., Devonshire, A.L., Warmke, J.W., Usherwood, P.N., Cohen, C.J. J. Gen. Physiol. (2000) [Pubmed]
  18. Functional and evolutionary consequences of pyrethroid resistance mutations in S6 transmembrane segments of a voltage-gated sodium channel. Zhao, Y., Park, Y., Adams, M.E. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  19. A valine421 to methionine mutation in IS6 of the hscp voltage-gated sodium channel associated with pyrethroid resistance in Heliothis virescens F. Park, Y., Taylor, M.F., Feyereisen, R. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  20. SNARE-complex disassembly by NSF follows synaptic-vesicle fusion. Littleton, J.T., Barnard, R.J., Titus, S.A., Slind, J., Chapman, E.R., Ganetzky, B. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  21. Regulation of neuronal excitability through pumilio-dependent control of a sodium channel gene. Mee, C.J., Pym, E.C., Moffat, K.G., Baines, R.A. J. Neurosci. (2004) [Pubmed]
  22. The DSC1 channel, encoded by the smi60E locus, contributes to odor-guided behavior in Drosophila melanogaster. Kulkarni, N.H., Yamamoto, A.H., Robinson, K.O., Mackay, T.F., Anholt, R.R. Genetics (2002) [Pubmed]
  23. Neurophysiological defects in temperature-sensitive paralytic mutants of Drosophila melanogaster. Siddiqi, O., Benzer, S. Proc. Natl. Acad. Sci. U.S.A. (1976) [Pubmed]
  24. Analysis of anesthetic action on the potassium channels of the Shaker mutant of Drosophila. Tinklenberg, J.A., Segal, I.S., Guo, T.Z., Maze, M. Ann. N. Y. Acad. Sci. (1991) [Pubmed]
  25. Developmentally regulated alternative splicing generates a complex array of Drosophila para sodium channel isoforms. Thackeray, J.R., Ganetzky, B. J. Neurosci. (1994) [Pubmed]
  26. Transcription analysis of the para gene by in situ hybridization and immunological characterization of its expression product in wild-type and mutant strains of Drosophila. Amichot, M., Castella, C., Bergé, J.B., Pauron, D. Insect Biochem. Mol. Biol. (1993) [Pubmed]
  27. The molecular interactions of pyrethroid insecticides with insect and mammalian sodium channels. Vais, H., Williamson, M.S., Devonshire, A.L., Usherwood, P.N. Pest Manag. Sci. (2001) [Pubmed]
  28. Neurogenetic analysis of Drosophila mutations affecting sodium channels: synergistic effects on viability and nerve conduction in double mutants involving tip-E. Ganetzky, B. J. Neurogenet. (1986) [Pubmed]
  29. Sodium current density correlates with expression of specific alternatively spliced sodium channel mRNAs in single neurons. O'Dowd, D.K., Gee, J.R., Smith, M.A. J. Neurosci. (1995) [Pubmed]
 
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