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

• Pumilio is sufficient to influence para mRNA [21].

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

• We have used a combination of RNA-PCR and sequence analysis to examine a 1.7 kilobase region of the para mRNA that encompasses the previously reported sites of alternative splicing [25].
• 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 [26].
• Recent progress in the cloning of alpha (para) and beta (TipE) Na channel sub-units from Drosophila melanogaster (fruit fly) and Musca domestica (housefly) have facilitated functional expression studies of insect Na channels in Xenopus laevis oocytes, assayed by voltage clamp techniques [27].
• In previous work it was shown that parats (paralyzed, temperature-sensitive, 1-53.9) and napts (no action potential, temperature-sensitive, 2-56.2), two temperature-sensitive paralytic mutations that block nerve conduction at restrictive temperatures, interact synergistically in double mutants causing unconditional lethality [28].
• We have examined the role of alternative splicing within the first cytoplasmic loop of the Drosophila sodium channel gene para in regulating sodium current expression, using single-cell RT-PCR [29].

References