bss, sbl, bang senseless, olfD, smellblind
α-subunit of voltage-gated sodium channel - neuromuscular junction - required for locomotor activity - generates sodium-dependent action potentials - regulated by RNA alternative splicing and translational repression
Multiphase exon postulated: exon reading frame differs in alternative transcripts (FBrf0209044); overlap >20aa.
Gene model reviewed during 5.55
Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.
Gene model reviewed during 5.44
Stop-codon suppression (UGA) postulated; FBrf0216884.
Gene model reviewed during 5.51
Gene model reviewed during 5.56
3.0 (northern blot)
The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\para using the Feature Mapper tool.
GBrowse - Visual display of RNA-Seq signalsView Dmel\para in GBrowse 2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Source for identity of: Shudderer Shu
Sensitivity of para to DDT is not lowered by the 'super-kdr' mutation M918T, although this is reduced 10-fold by the 'kdr' mutation L1014F.
RNAi generated by PCR using primers directed to this gene causes a cell growth and viability phenotype when assayed in Kc167 and S2R+ cells.
RNAi screen using dsRNA made from templates generated with primers directed against this gene causes a cell growth and viability phenotype when assayed in Kc167 and S2R+ cells.
para transcripts undergo adenosine-to-inosine RNA editing via a mechanism that apparently requires dsRNA secondary structure formation encompassing the edited exon and the downstream intron. The mlenap-ts1 mutation results in the occurrence of a "splicing catastrophe" of the para transcript in the region of the RNA editing site; more than 80% of para transcripts in this background are aberrant, owing to internal deletions that include the edited para exon.
Rearing parats1 embryos, at restrictive temperatures, starting at different times during synaptogenesis, reveals neural activity at a certain period of development profoundly affects the distribution of GluRIIA receptors.
Heterologous expression of para sodium channels in Xenopus oocytes is poor. Coexpression of para with tipE results in robust sodium currents. The biophysical and biochemical properties of invertebrate and vertebrate neuronal sodium channels are distinct.
The region that includes para contains a complex of neurally expressed genes, Cnx14D, Arp14D, Pp2B-14D and Cap. These five genes may represent a functionally related group sharing some coordinate regulatory mechanism.
The role of alternative splicing of the para gene in regulating sodium current expression has been investigated.
The pattern of expression of para throughout development has been analysed.
The "sbl" alleles represent a class of para alleles, and define a novel class of sodium channel mutation.
The genomic organisation of the para locus has been analysed. A number of developmentally regulated alternative splice products have been identified.
Distribution of para transcripts and protein studied in wild type and mlenap-ts1 mutants, where amount of para product is reduced.
Ion channel mutants alter synaptic activity at the embryonic neuromuscular junction (NMJ). GluRIIA expression in the postsynaptic membrane is reduced by changes in presynaptic electrical activity. Synaptic transmission is blocked in para mutants in a temperature-dependent manner. Presynaptic electrical activity during embryonic synaptogenesis is constitutively required for GluRIIA expression at the NMJ and to induce receptor clustering at the NMJ. The size of the synaptic domain depends on the level of neural activity during embryonic synaptogenesis.
Mutant analysis of para (unspecified) provides evidence for the participation of a G0-like protein in learning and memory. Sex-dependent enhancement in pertussis toxin catalysed ADP-ribosylation with respect to wild type: attributed in part to an increase in the α subunit of the G0-like protein.
The olfactory phenotypes of para mutants has been studied with respect to courtship behaviour.
Changes in the level of para+ expression can strongly influence neuronal excitability.
Mutations of para cause abnormalities in the electroretinogram (ERG) and/or prolonged depolarization after potential (PDA).
Viable alleles of para perform aberrantly in multiple olfactory paradigms as both larvae and adults.
A cDNA that probably corresponds to the para locus has been cloned and sequenced.
The para locus encodes an essential function. Genetic, electrophysiological, behavioral and pharmacological studies of mle and para mutants suggest that they effect sodium channels and the genes may encode different subunits.
Mutations of para have been recovered both as a consequence of their paralytic phenotype (as para) and as a consequence of their olfactory phenotype (as sbl). For the para alleles: exposure to 29-30oC causes rapid paralysis that is quickly reversed on shift to 22-25oC. Larvae are paralyzed, too, at somewhat higher temperatures. Flies of some para strains seem sluggish at lower temperatures. When these mutants are still paralyzed (i.e. at high temperatures), they appear to retain many of their 'vital functions,' their heart still beats (Grigliatti, Suzuki and Williamson, 1972) and they quickly regain normal behavior when shifted to 22oC after several hours at 29oC (Suzuki, Grigliatti and Williamson, 1971); in fact, after a less prolonged exposure (30 min) to high temperature, the still-heated mutant flies regain weak mobility and are even able to right themselves and walk (Suzuki, Grigliatti and Williamson, 1971). parats1/+ adults become paralyzed at 40oC within one min <up>10 min required to paralyze wild-type (Hall, 1973)</up>. parats1 larvae stop 'tracking' at high temperature (Wu, Ganetzky, Jan, Jan and Benzer, 1978). parats1 is nearly unconditionally lethal when uncovered by a deletion or other para-locus aberration, whereas other alleles lead to reduced viability (unconditional) when heterozygous with chromosomal aberrations at the locus (Ganetzky, 1984). Action potentials in larval nerves are reversibly temperature-sensitive (Wu and Ganetzky, 1980) and the same can be inferred for at least some adult neurons (indicated by brain stimulation and recording of responses in thoracic muscles (Siddiqi and Benzer, 1976; Benshalom and Dagan, 1981). Other 'excitable phenomena,' such as the electroretinogram responses and synaptic transmission, appear to be normal in parats1 adults at high temperature (Suzuki, Grigliatti and Williamson, 1971; Siddiqi and Benzer, 1976); also parats1 does not block action potentials in the cervical giant fiber at high temperature (Nelson and Baird, 1985) in contrast to results of recording from larval motor neurons (Wu and Ganetzky, 1980); other studies of the giant fiber pathway (involving adult mosaics bilaterally split, externally, for parats1 and para+) indicate that at least certain elements of the pathway (if not the giant fiber itself) fail to fire action potentials at elevated temperature (Benshalom and Dagan, 1981) and recordings from mosaics of this type also suggest 'functional coupling' between left and homologous right sides of this giant fiber pathway (Benshalom and Dagan, 1985). parats1 causes first larval instar death when in combination with mlenap-ts1 (Wu and Ganetzky, 1980; Ganetzky, 1984); similar lethality occurs when para+ dosage is decreased in a mlenap-ts1 background (Ganetzky, 1984). Other para alleles, in combination with mlenap-ts1, lead to reduced viability, with parats115 having the strongest effect, followed by paraST76 and paraST109 (Ganetzky, 1984). In combination with the tipE mutation, para mutations again cause decreased viability, but the allele-specific interactions are different from those of the series just noted <up>i.e. with respect to mlenap-ts1 (Ganetzky, 1986)</up>. Surviving para; tipE double mutants are weak and show accentuated heat-sensitivity (in regard to mobility and nerve conduction); para alleles are dominant for behavioral defects in a homozygous tipE background (Ganetzky, 1985). In adults doubly mutant for parats1 and mlenap-ts1, sensory cells (developing from imaginal discs in mosaics) appear to have no nerve conduction (Burg and Wu, 1984). In mosaics involving para mutations only one allele (paraST109) causes all legs to be either paralyzed or normal in different individual gynandromorphs (Siddiqi and Benzer, 1976), in contrast to independent paralysis of legs in mosaics constructed with respect to parats1 (Grigliatti, Suzuki and Williamson, 1972; Siddiqi and Benzer, 1978). These results (and others, e.g. Benshalom and Dagan, 1985), reveal poor correlation of the externally mutant genotype (in mosaics) and behavioral or physiological malfunctions <up>consistent with internal (no doubt neural) 'foci' for para's action</up>. In other studies, parats1 mosaics with mutant heads (scored externally) usually are immobile at high temperature, but maintain normal posture (Suzuki, Grigliatti and Williamson, 1971; Grigliatti, Suzuki and Williamson, 1972). Exposure of parats1 males to high temperature causes arrest of the oscillator underlying rhythmic component of courtship song (Kyriacou and Hall, 1985). At permissive tempe
dominant cold-sensitive, reversible paralytic; heterozygous mutant females begin uncoordinated behavior (progressively: abnormal leg movements, leg stretching, wing fluttering) on shift from 25oC to 18-20oC; paralysis eventually occurs, and recovery is gradual on shift back to higher temperatures; critical temperature to include the debilitations is ca. 2oC lower from Ocd7 than for other alleles; also males hemizygous for Ocd7 have better viability than those expressing the other alleles, with Ocd4 being the most severely affected i.e., nearly lethal (Ocd4 also causes near lethality when heterozygous with any of the other alleles); at 25oC, mutant males walk in reeling manner and fall over frequently; none can fly and attempts to coax jumps (to initiate flight) cause the males merely to fall over when touched; these phenotypes also seen in homozygotes and heteroallelic combinations; certain of the homozygous mutant females (e.g. Ocd2 and Ocd3) hold their wings in drooped position; also seen in Ocd1 males; this phenotype also observed in Ocd2/+ and Ocd3/+ females, which also walk in unsteady manner; other alleles, when heterozygous, allow for seemingly normal behavior at 25oC, except that their legs shake under etherization (with Ocd4 causing the strongest aberrant shaking). Abrupt, anomalous changes in Arrhenius activation energy of the mitochondrial enzyme, succinate cytochrome c reductase, are seen at temperatures close to those which induce paralysis (Sondergaard et al. 1975). Two-dimension gels of mitochondria isolated from Ocd1 contain an additional polypeptide not seen in extracts of wild-type (Sondergaard, 1986).
Separable by recombination from eas, which causes a similar phenotype and to which bss is closely linked.
Mechanical shock or vortexing induces paralysis lasting for 2-3 minutes; heterozygous female are paralysed for 40-50 seconds. Homozygotes and hemizygotes have abnormally prolonged release of neurotransmitter at larval neuromuscular junctions, which is associated with multiple firing of action potentials in the nerves; behavioral and electrophysiological phenotypes suppressed by mlenap-ts1 at its permissive (low) temperature.