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General Information
Symbol
Dmel\parats1
Species
D. melanogaster
Name
FlyBase ID
FBal0013491
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
parats, parats-1
Key Links
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference

Mutation is in the third intron.

Mutation within the intracellular S4-S5 linker, in domain I.

Expression Data
Reporter Expression
Additional Information
Statement
Reference
 
Marker for
Reflects expression of
Reporter construct used in assay
Human Disease Associations
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 0 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
ameliorates  epilepsy
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

parats1 homozygous adults exhibit fully penetrant paralysis 120sec after being shifted to 38[o]C temperature.

No paralysis is seen in parats1/+ mutant flies in response to elevated temperatures.

When reared continuously at 22[o]C, neuromuscular junction size increases at a constant rate in mutant larvae, as occurs in wild type. However, when the are shifted to 29[o]C, NMJ size remains constant in the mutants, in contrast to the increase in size seen in wild type.

parats1 mutants suppress temperature-induced synaptic outgrowth.

In controls, high K[+] stimulation results in the formation of "ghost boutons" - boutons containing synaptic vesicles but lacking active zones and presynaptic structures. But blocking action potentials in neurons by shifting parats1 larvae to restrictive temperatures prevents this.

parats1/Y males and parats1/para60 females are significantly more sensitive to isoflurane than control flies; the latency between nerve shock and excitatory junctional potential onset at the neuromuscular junction treated is significantly larger in the mutant flies than in controls following treatment with isoflurane.

parats1 flies are completely paralysed at 38[o]C.

parats1 homozygotes are viable but exhibit paralysis following heat shock. parats1/paraJS1 flies are also viable but do not exhibit paralysis following heat shock.

Neither parats1 nor parats1/parats115 flies show a significantly shortened lifespan. However, the brains of these flies show neurodegeneration. parats1 flies become instantly paralyzed upon exposure to a 3 minute 38oC heat shock, but recover instantly when transferred to 22oC.

parats1 flies are hypersensitive to isoflurane; isoflurane increases the delay from the stimulus to the onset of synaptic currents in both wild-type and mutant flies but the delay in response to isoflurane is increased in mutant axons compared to controls.

sesB1/parats1 double mutants display no significant paralysis after heat shock (90s, 30[o]C) and vortexing (10s).

Atpα2206/parats1 double mutants display no significant paralysis after heat shock (90s, 30[o]C) and vortexing (10s).

parats1 mutants paralyse within seconds of exposure to 38o.

parats1 mutant flies show flaccid paralysis when exposed to 300C for 2 minutes.

Mutant flies show a rapid onset of paralysis when placed at 38oC.

Like wild-type larvae, parats1 mutants exhibit an increase in quantal content and enhanced locomotor activity when moved from a food slurry environment at 18oC to an agar plate at 22oC. When the temperature is shifted to 34oC for 20 minutes and maintained at 29oC after this, parats1 larvae become paralysed, while wild-type larvae continue to show enhanced locomotion. After two hours of paralysis, quantal content levels of the parats1 mutants drop to those seen at 18oC on the food slurry, while wild-type quantal content (following two hours of enhanced activity) is higher than at 22oC. During the two hours at 29oC, wild-type larvae show an increase in the number of large subsynaptic eIF-4E aggregates, while the amount of aggregates remain unchanged in the parats1 mutants.

Injection of 5-HT or norepinephrine increases the heart rate in parats1 mutant flies at 30oC, and the change in rate is no different from that seen in wild-type controls. Injection of acetylcholine does no result in a significant change in heart rate in parats1 mutant flies at 30oC (in contrast to wild-type controls which show an increase in heart rate when injected with acetylcholine). Injection of dopamine or octopamine increases the heart rate in parats1 mutant flies at 30oC, but the increase is significantly less than that seen in wild-type controls.

Spike-like potentials are seen when local field potential (LFP) recordings are made from the differential activity between one electrode place in between the mushroom bodies at approximately the level of the base of the calyces versus one placed in the lamina or medulla of the optic lobes. These spike-like potentials are significantly suppressed in parats1 in flies subjected to heat shock at 38oC for 30 seconds, but are normal in flies kept at 25oC.

Life span at 28oC is essentially the same as wild-type controls.

Mutant flies are paralysed at 27oC.

parats1 flies treated with sodium valproate (NaVP) do not show a reduction in body weight, in contrast to wild-type flies. Treatment of parats1 flies with NaVP causes an increase in mortality as is seen in wild-type flies.

The production of wing abnormalities induced by valproate in wild-type flies is suppressed by the parats1 mutation.

Flies are sensitive to ether (lower concentrations are required for anaesthesia compared to wild-type flies).

Shows no temperature sensitive ERG on/off transients mutant phenotype.

The difference in courtship song interpulse interval between parats1 and wild-type males shows a significant positive correlation with temperature, while the difference in courtship song amplitude between parats1 and wild-type males shows a significant negative correlation with temperature.

Homozygous flies show significant resistance to dichloro-diphenyl-trichloro ethane (DDT) compared to wild-type flies.

Temperature sensitive block or decrease is synaptic transmission at the neuromuscular junctions. Embryos shifted to restrictive temperature of 32oC at 12hr AEL and kept at this temperature for the remainder of embryogenesis show no spontaneous movement nor were their tracheae inflated. Muscle pattern formation and shortening of the ventral nerve cord (VNC) is normal. Glutamate receptor clusters are found at the extrajunctional region, these are not seen in wild type embryos. Embryos reared at 30oC show a few clusters at the extrajunctional region and some at the synaptic site. These embryos show low spontaneous movement and few hatch. At 25oC receptors in the extrajunctional region disappear and are localised at te synaptic site. Embryos develop and hatch normally. 10hr heat shock at 34oC after 12hr AEL causes receptor accumulation at the extrajunctional region. The number of receptor clusters increases at higher temperatures. Neural activity is required for receptor accumulation.

Temperature sensitive paralysis threshold is 32oC. Flies become paralysed within 15 seconds of a temperature shift to 39oC and recover completely within 15 seconds of shifting back to room temperature.

Sub-anaesthetic concentration of carbon dioxide enhances the paralytic phenotype.

Mutation has no effect on larval heartbeat at temperatures between 20oC and 37.5oC.

Homozygous larvae raised at the restrictive temperature (37oC for 6 hours/day from late embryogenesis through to third larval instar) do not show an increased frequency of ectopic neuromuscular synapses, but do show an increased frequency of ectopic neuromuscular synapses if the larvae are also mutant for tipEunspecified. Embryos raised at 34oC show an increased frequency of immature filopodial contacts on muscle fibres 6 and 7 ("collateral sprouts") compared to wild-type embryos raised at 34oC.

Homozygotes show increased sensitivity to halothane, chloroform and trichloroethylene in an inebriometer assay (an assay of geotactic and postural behaviour) compared to wild-type flies. Decapitated flies lose the halothane sensitive phenotype.

The delivery of an electrical buzz (50-400 msec) to the brain has no significant effect on parats1 mutant flies.

Lethal over parasbl-3 and parasbl-4. parats1 flies show a normal larval olfactory response to propionic acid at dilutions spanning three orders of magnitude. Transheterozygotes with parasbl-1, parasbl-2, parasbl-5 and parasbl-6 show normal olfactory response to 10-1 propionic acid. Transheterozygotes of parats1 with parasbl-1, parasbl-5 and parasbl-6 show a significant increase in temperature sensitive paralysis compared to parats1/+ controls.

Adults are reversibly paralysed at 29oC, at this temperature nerve conduction at the neuromuscular junction (NMJ) appears to be completely blocked. parats1/Df(1)D34 transheterozygotes die as first instar larvae. Homozygous embryos maintain periodic bursting activity with an excitatory junction current (EJC) amplitude similar to wild type, but bursting frequency and EJCs per burst are significantly reduced. Embryos hatch at 30oC but show a dramatic reduction in hatching efficiency at 32oC. Nerve conduction at the embryonic NMJ is reduced at 30oC, nearly suppressed at 32oC and blocked at 34oC. Embryos reared at 34oC for 8 hours from the onset of synaptogenesis exhibit distribution of glutamate receptors on the muscle, not localised at the NMJ. A shift in temperature mid-synaptogenesis does not affect receptor clustering at the NMJ. Synaptic morphology, at the light microscope level, of embryonic NMJs raised at the restrictive temperature is not significantly different from wild type. These hypoactive synapses occupy a smaller area of the muscle surface relative to wild type causing increased synaptic density (the branch and bouton numbers are not altered).

parats1 mlenap-ts1 double mutant bristle sensory cells in small-patch mosaic flies have normal branching and terminal arborisation patterns in the central nervous system.

Double mutants with mlenap-ts1 or parats1 show no exaggeration of the paralytic phenotypes, nor any efect on their viability and fertility. These results suggest stmA does not interact with para or mle.

Flies become paralysed at 29oC.

Flies become paralysed at 29-31oC. The long-latency response of the dorsal longitudinal muscle disappears abruptly as the temperature is increased to 31 +/- 1oC, although the short-latency response is normal.

The temperature at which mutant flies become paralysed is dependent on the rearing temperature; flies raised at a low temperature (8oC) become paralysed at a lower temperature than flies raised at a high (30oC) temperature. Temperatures up to 7oC above the paralytic temperature usually do not block the dorsal longitudinal muscle response to giant fibre stimulation. The jump muscle response is variable at this high temperature, some flies have a normal response, some have no response at all, and some have a reduced amplitude response. The interval from brain stimulation of the giant fibre to a response in the DLM or jump muscle is longer than in wild-type flies at all temperatures. Both the DLM and the jump muscle have a weaker following frequency than wild-type, which can be rescued by injecting 4-aminopyridine into mutant flies.

Reversible paralysis at 25oC.

Dissociated central nervous system cultures from parats1 larvae appear morphologically normal and cells have a similar survival rate to wild-type at both 22oC and at the restrictive temperature of 35oC. parats1 cell cultures show a significantly higher resistance to veratridine than wild-type cells at 22oC, although the resistance is not as high as for mlenap-ts1 cells. At 35oC, the resistance of parats1 cells to veratridine increases to a level similar to mlenap-ts1 cells.

Homozygous or hemizygous adults show normal walking and flying ability at 22oC to 25oC, but at higher temperatures become increasingly debilitated, and become completely paralysed in less than 5 seconds when shifted to 29oC. This paralysis is reversible; mobility is recovered in less than 2 seconds when paralysed flies are shifted back to 22oC. Paralysis and recovery can be induced repeatedly in the same individuals with no apparent harm. Although paralysis is initially complete at 29oC, some recovery of movement is seen in flies kept at 29oC, and after 30 minutes at 29oC, flies can right themselves and have limited walking ability. Larval mobility is unaffected.

Marked reduction in number of embryonic neurons in cell culture expressing sodium currents in these alleles (O'Dowd et al., 1987; O'Dowd et al., 1989). temperature-sensitive

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference

parats1 has paralytic | adult stage | temperature conditional phenotype, enhanceable by Scer\GAL4sca.PU/Cnx99AKK108301

NOT Enhanced by
Statement
Reference

parats1 has paralytic | larval stage | heat sensitive phenotype, non-enhanceable by Ncc69r2

parats1 has paralytic | temperature conditional phenotype, non-enhanceable by awdCM47

parats1 has paralytic | temperature conditional phenotype, non-enhanceable by awdMSF15

parats1 has paralytic | temperature conditional phenotype, non-enhanceable by awdMSM95

parats1 has paralytic | heat sensitive phenotype, non-enhanceable by stnB6/stnA6

Suppressed by
Statement
Reference

parats1 has abnormal neuroanatomy | temperature conditional phenotype, suppressible by Syt4BA1

Enhancer of
Statement
Reference

para[+]/parats1 is an enhancer of paralytic | adult stage phenotype of CsasMB04236

para[+]/parats1 is an enhancer of paralytic | heat sensitive phenotype of SiaTS23

para[+]/parats1 is an enhancer of short lived | dominant phenotype of AtpαDTS1

Suppressor of
Statement
Reference

parats1 is a suppressor of abnormal neurophysiology | heat sensitive phenotype of SwgX118

parats1 is a suppressor of abnormal neurophysiology | heat sensitive phenotype of MhcS2

parats1 is a suppressor of abnormal neurophysiology | heat sensitive phenotype of Mhc5

parats1 is a suppressor of abnormal neurophysiology | heat sensitive phenotype of MhcS1

parats1 is a suppressor of abnormal neurophysiology | heat sensitive phenotype of BrkdJ29

parats1 is a suppressor of paralytic | conditional phenotype of Atpα2206

parats1 is a suppressor of paralytic | conditional phenotype of sesB1

Other
Phenotype Manifest In
Enhanced by
Statement
Reference

parats1 has adult brain phenotype, enhanceable by AtpαDTS1/Atpalpha[+]

parats1 has phenotype, enhanceable by Khc4

parats1 has phenotype, enhanceable by Khc5

Suppressed by
Statement
Reference

parats1 has neuromuscular junction | temperature conditional phenotype, suppressible by Syt4BA1

Enhancer of
Statement
Reference

para[+]/parats1 is an enhancer of adult brain phenotype of AtpαDTS1

Suppressor of
Statement
Reference

parats1 is a suppressor of neuromuscular junction | temperature conditional phenotype of Syt4BA1

parats1 is a suppressor of NMJ bouton | temperature conditional phenotype of Syt4BA1

parats1 is a suppressor of indirect flight muscle | heat sensitive phenotype of SwgX118

parats1 is a suppressor of indirect flight muscle | heat sensitive phenotype of MhcS2

parats1 is a suppressor of indirect flight muscle | heat sensitive phenotype of Mhc5

parats1 is a suppressor of indirect flight muscle | heat sensitive phenotype of MhcS1

parats1 is a suppressor of indirect flight muscle | heat sensitive phenotype of BrkdJ29

Other
Additional Comments
Genetic Interactions
Statement
Reference

The paralysis phenotype of parats1 homozygotes induced by temperature shift to 38[o]C is significantly enhanced by the expression of Cnx99AKK108301 under the control of Scer\GAL4sca.PU, as shown by a slower recovery from paralysis upon return to room temperature, but is not significantly suppressed by the expression of Cnx99AScer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4sca.PU.

One copy of parats1 enhances the paralysis phenotype seen in homozygous CsasMB04236 mutant flies at elevated temperatures. Onset of paralysis occurs earlier than in CsasMB04236 mutants alone.

The reduction in neuromuscular junction size seen in parats1 larvae at 29[o]C is suppressed by expression of LanAC01-190 under the control of Scer\GAL4C57.

The severity of the temperature sensitive paralytic phenotype seen in ST6GalS23/ST6GalS23 flies is enhanced by parats1/+; the time for onset of paralysis at 38[o]C is reduced in the double mutant flies compared to the single mutant.

Synaptic outgrowth induced by expression of Syt4wt.Scer\UAS under the control of Scer\GAL4Mhc.PW is dramatically reduced in a parats1 background when animals are reared at 31[o]C compared with 25[o]C.

The short lived phenotype of AtpαDTS1 heterozygotes is enhanced in parats1/+ flies. parats1; AtpαDTS2 double mutants also have a short lifespan of <1 week. In addition to a shorter lifespan, parats1/+; AtpαDTS1/+ double mutants show an increase in the severity of spongiform neuropathology of the brain at 16 days compared to brains from parats1/+ or AtpαDTS1/+ single mutants. These double mutants show no significant change in temperature sensitivity compared to the single mutants. Like AtpαDTS1 single mutants, parats1; AtpαDTS1 mutants need several minutes to recover from a 3 minute 38oC heat shock.

The characteristic contraction of Ca-P60Aunspecified larvae that is seen at the restrictive temperature for Ca-P60Aunspecified is abolished in Ca-P60Aunspecified ; parats1 double mutants if the double mutants are at a temperature that is restrictive for both Ca-P60Aunspecified and parats1, but is still seen if the double mutants are at a temperature that is restrictive for Ca-P60Aunspecified but permissive for parats1.

Suppression of Mhc5 seizure activity is observed in parats1 Mhc5/+ double mutant hemizygous males at 38oC.

comt6 parats1; Ca-P60AKum170 triple mutants do not show spontaneous DLM firing activity at 330C like comt6 and Ca-P60AKum170 single mutants, but these triple mutants do show an increase of activity when shifted to 400C, the restrictive temperature for parats1 mutants.

comt4, parats1 double mutant animals exposed to 38oC for 5 minutes show a rapid recovery from the paralysis phenotype when returned to the permissive temperature. After rapid recovery and normal behaviour, these flies suddenly re-paralyse several minutes later at the permissive temperature.

79% of parats1 flies expressing two copies of P{UAS-EKO+} (driven by Scer\GAL4A307) fail to expand their wings.

Flies that are also Khc6/KhcBD show synthetic lethality.

Shows unconditional lethality when double mutant with mlenap-ts1. Lethality is evident even when the flies are grown at 18oC. Lethality acts before pupation, mostly in the larval stages. parats1 shows dominant effects on both behavior and viability in an mlenap-ts1 background.

Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Partially rescues

parats1 partially rescues paraShu/para[+]

Comments

paraShu/parats1 transheterozygous female adults reared at 25[o]C temperature exhibit strong decreases in wing posture defects and in the movement time spent in the centre of a circular space, as compared to paraShu heterozygous females.

Images (0)
Mutant
Wild-type
Stocks (1)
Notes on Origin
Discoverer
Comments
Comments

Order of sensitivity to ether anaesthesia is (most sensitive to least sensitive): parahd8 > parats3 > parats1. Order of sensitivity to heat induced paralysis is (lower temperature for 50% paralysis to higher temperature for 50% paralysis): parats3 > parats1 > parahd8.

Mosaic analysis shows that para+ head tissue is necessary for normal leg movement, and para+ thorax and leg tissue is required for the posture and normal movement of each leg.

Does not suppress the Sh behavioural phenotype.

A haplo-specific lethal mutation.

Complements nonA9 in females heterozygous for both mutations.

dnc1, parats1 and dnc1, shi1 double mutants show no more severe effect than either paralytic mutant alone. The parats1, stnA7 double mutant is no more inviable than stnA7 alone.

At 32oC postsynaptic GluRIIA expression is reduced and absent at 34oC.

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (6)
References (84)