FB2024_03 , released June 25, 2024
Allele: Dmel\SERCAKum170
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General Information
Symbol
Dmel\SERCAKum170
Species
D. melanogaster
Name
FlyBase ID
FBal0184441
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
Kum170, CaP60AKum170, Ca-P60AKum170
Key Links
Genomic Maps

Allele class
Nature of the Allele
Allele class
Progenitor genotype
Cytology
Description

Amino acid replacement: E442K.

Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Nucleotide change:

G23931225A

Amino acid change:

E442K | SERCA-PA; E442K | SERCA-PB; E442K | SERCA-PC; E442K | SERCA-PD; E442K | SERCA-PE; E442K | SERCA-PF; E442K | SERCA-PG; E442K | SERCA-PH; E442K | SERCA-PI

Reported amino acid change:

E442K

Comment:

Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.

Variant Molecular Consequences
Associated Sequence Data
DNA sequence
Protein sequence
 
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 ( 0 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

SERCAKum170 heterozygotes do not show flight defects.

Ca-P60AKum170 mutant fat body cell clones have fewer and smaller lipid droplets than adjacent control cells. In addition, the mutant cells are smaller than the surrounding wild type cells. The salivary glands in Ca-P60AKum170 mutants are similar in size to wild type.

Unlike in wild type, all heterozygous Ca-P60AKum170 mutant flies subjected to 7 or 10 minute heat shocks develop paralysis. 20% of flies exposed to a five minute heat shock undergo paralysis. The flies that develop paralysis do not recover normal function until 72 hours after shock. Heat rate is reduced and is inversely proportional to the length of the heat shock. End diastolic dimension is increased but there is no effect on fractional shortening.

Synapse strength (neurotransmitter release per action potential) is increased compared to wild type at muscle 6/7 neuromuscular junctions in mutant larvae.

Larval neurons heterozygous for Ca-P60AKum170 exhibit elevated levels of basal cytosolic Ca[2+].

After depolarisation with 70mM KCl, neurons cultured from Ca-P60AKum170/+ larvae return to basal intracellular Ca[2+] levels is slower than in neurons cultured from wild-type larvae.

Heterozygous adults paralyse within 3 minutes between 39o and 40oC. Heterozygous larvae also paralyse at 40oC within 5 minutes and the paralysed larvae appear shortened due to severe contraction of the body wall muscles. Most homozygous embryos develop normally and hatch into very sluggish first instar larvae. Ca-P60AKum170 larvae exposed to 40oC for 15 minutes show an increased peak of presynaptic Ca2+ levels at the neuromuscular junction in response to a 4 minute burst of 30Hz nerve stimulation compared to wild-type animals and a rapid return to baseline levels of Ca2+ after cessation of stimulation (in contrast to wild-type animals where the levels of presynaptic Ca2+ remain significantly elevated 2 minutes after the cessation of stimulation). Third instar Ca-P60AKum170 larvae exposed to 40oC show a significant reduction in evoked but not spontaneous release at the neuromuscular junction. Spontaneous activity in the dorsal longitudinal muscles (DLMs) of Ca-P60AKum170 adults at the permissive temperature is similar to that seen in wild-type adults. However, after a 5 minute exposure to 40oC, Ca-P60AKum170 DLMs show characteristic broad multipeaked action potentials which progress eventually to spike failure (this phenotype is not seen in wild-type adults exposed to 40oC). Ca-P60AKum170 DLM fibres that have not been exposed to 40oC show frequent action potential failures at a stimulation frequency of 30Hz (in contrast to wild-type fibres which do not show failures in response to stimulation). Ca-P60AKum170 DLM fibres that have been exposed to 40oC show failures at a stimulation frequency of 10Hz. At a given frequency of stimulation, failures are seen earlier in heated Ca-P60AKum170 animals than in unheated Ca-P60AKum170 animals. Voltage gated calcium currents in muscles are dramatically and chronically reduced in heated Ca-P60AKum170 animals, while unheated Ca-P60AKum170 animals have calcium currents that are comparable to wild type.

When Ca-P60AKum170 mutants are exposed to 400C for 4 minutes they show paralysis for up to 48 hours. During this time, the flies show uncoordinated twitches, muscle contraction, and infrequent but intense bouts of seizure-like behavior followed by a return to paralysis. At 200C, Ca-P60AKum170 mutants show wild-type levels of DLM activity. However, after 4 minutes of exposure to non-permissive temperatures, DLM of these mutants show infrequent bursts of spontaneous activity.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Statement
Reference
NOT suppressed by
Statement
Reference

Itprwc361/Itprug3, Orai[+]/Oraik11505, SERCA[+]/SERCAKum170 has abnormal flight phenotype, non-suppressible by NUCB1c01508/NUCB1[+]

SERCAKum170 has paralytic | dominant phenotype, non-suppressible by RyR16/RyR[+]

Suppressor of
Statement
Reference

SERCA[+], NUCB1c01508, SERCAKum170, NUCB1[+] is a suppressor of increased mortality during development | cold sensitive phenotype of Itprwc703/Itprug3

SERCA[+], NUCB1c01508, SERCAKum170, NUCB1[+] is a suppressor of increased mortality during development | cold sensitive phenotype of Itprwc361/Itprug3

Ca-P60A[+]/SERCAKum170 is a suppressor of flightless | partially phenotype of Gα49B[+]/Gαq221c, Itprwc703/Itprwc361

Ca-P60A[+]/SERCAKum170 is a suppressor of flightless | partially phenotype of Gα49B[+]/Gαq221c, Itprwc703/Itprwc361, Plc21Ck31911/Plc21C[+]

Ca-P60A[+]/SERCAKum170 is a suppressor of abnormal neurophysiology phenotype of Gα49B[+]/Gαq221c, Itprwc703/Itprwc361

Ca-P60A[+]/SERCAKum170 is a suppressor of abnormal neurophysiology phenotype of Gα49B[+]/Gαq221c, Itprwc703/Itprwc361, Plc21Ck31911/Plc21C[+]

Ca-P60A[+]/SERCAKum170 is a suppressor of lethal | cold sensitive phenotype of Itprug3/Itprka1091

Ca-P60A[+]/SERCAKum170 is a suppressor of flightless | partially phenotype of Itprug3/Itprka1091

NOT Suppressor of
Other
Phenotype Manifest In
Suppressed by
NOT Enhancer of
Statement
Reference
Suppressor of
Statement
Reference

Ca-P60A[+]/SERCAKum170 is a suppressor of wing phenotype of Gα49B[+]/Gαq221c, Itprwc703/Itprwc361

Ca-P60A[+]/SERCAKum170 is a suppressor of wing phenotype of Gα49B[+]/Gαq221c, Itprwc703/Itprwc361, Plc21Ck31911/Plc21C[+]

Ca-P60A[+]/SERCAKum170 is a suppressor of wing phenotype of Itprug3/Itprka1091

Other
Additional Comments
Genetic Interactions
Statement
Reference

SERCAKum170, Oraik11505 double heterozygotes do not show flight defects.

RyR16 partially suppresses the phenotypes seen in heterozygous Ca-P60AKum170 mutant flies in response to heat shock. The paralysis is still present but the increase in heart rate and defect in cardiac function are both suppressed. End diastolic dimensions and fractional shortening are also unchanged compared to Ca-P60AKum170 alone.

Expression of two copies of Ca-P60Awt.tinC significantly rescues the cardiac function phenotype seen in wupAhdp-2 mutant flies. Heart rate is still reduced.

comt6 Ca-P60AKum170 double mutants exhibit increased synapse growth and transmitter release.

Scer\GAL4OK6-driven motor neuron-limited expression of NFATEP19579 or NFATEP1508 completely abolishes increased synapse growth and transmitter release observed in comt6 Ca-P60AKum170 double mutants.

comt6 Ca-P60AKum170 double mutant flies show increased locomotor activity compared to wild-type controls.

The average number of synaptic boutons at the muscle 6/7 neuromuscular junction is increased in comt6 Ca-P60AKum170 larvae compared to controls. In addition, synapse strength (neurotransmitter release per action potential) is increased compared to wild type, as is seen in each single mutant.

Expression of ShEKO.Scer\UAS.T:Avic\GFP-GL under the control of Scer\GAL4futsch-C380 suppresses the increased synaptic growth and transmitter release observed at the neuromuscular junction in comt6 Ca-P60AKum170 larvae.

Expression of either Ras85DN17.Scer\UAS or phlDN.Scer\UAS.cUa in motor neurons under the control of Scer\GAL4unspecified suppresses the increased synaptic growth and transmitter release observed at the neuromuscular junction in comt6 Ca-P60AKum170 larvae.

Expression of either kayFbz.Scer\UAS or CrebB-17AScer\UAS.b.cYa in motor neurons under the control of Scer\GAL4unspecified suppresses the increased synaptic growth and transmitter release observed at the neuromuscular junction in comt6 Ca-P60AKum170 larvae.

Larval neurons heterozygous for Ca-P60AKum170 in a Itp-r83Aka1091/Itp-r83Aug3 background exhibit elevated levels of basal cytosolic Ca[2+].

Ca-P60AKum170/olf186-FEY01467; Itp-r83Aka1091/Itp-r83Aug3 flies exhibit normal wings and normal levels of spontaneous electrical activity in DLM recordings. Flight ability is restored in a significant number of these triple mutant flies. Ca-P60AKum170/+; Itp-r83Aka1091/Itp-r83Aug3 mutants. Over 60% of olf186-Fk11505/Ca-P60AKum170; Itp-r83Aka1091/Itp-r83Aug3 adults and approximately 50% of olf186-FEY01467/Ca-P60AKum170; Itp-r83Aka1091/Itp-r83Aug3 adults pass as 'fliers' in the cylinder drop test assay. Air-puff delivery elicited sustainable rhythmic flight patterns similar to wild-type in a high proportion of these flies.

The presence of Ca-P60AKum170 has no effect on Ca[2+] release through the InsP[[3]]R on carbachol stimulation in Itp-r83Aka1091/Itp-r83Aug3 mutants.

The presence of olf186-FEY01467 in olf186-FEY01467/Ca-P60AKum170; Itp-r83Aka1091/Itp-r83Aug3 organisms restored carbachol-stimulated Ca[2+] release to wild-type levels.

The presence of a single copy of Ca-P60AKum170 delays Ca[2+] sequestration after carbachol-stimulated release, and leads to greater perdurance of the Ca[2+] peak; this effect of Ca-P60AKum170 is also present in cells derived from olf186-FEY01467/Ca-P60AKum170;Itp-r83Aka1091/Itp-r83Aug3 organisms.

Ca-P60AKum170 has a dominant effect and reduces levels of store Ca[2+] in all genotypes tested, including Ca-P60AKum170/+; Itp-r83Aka1091/Itp-r83Aug3 and Ca-P60AKum170/olf186-FEY01467; Itp-r83Aka1091/Itp-r83Aug3. Concurrent with the lower store, SOCE is greatly elevated in Ca-P60AKum170 heterozygotes. Significantly , SOCE is normal in neurons derived from Ca-P60AKum170/olf186-FEY01467; Itp-r83Aka1091/Itp-r83Aug3, as compared with single and double mutants.

The abnormal wing posture phenotype of Itp-r83Aka1091/Itp-r83Aug3 animals raised at 25'C is suppressed by Ca-P60AKum170/+. Lethality due to Itp-r83Aka1091/Itp-r83Aug3 in animals raised at 17'C is also suppressed by Ca-P60AKum170/+. The resulting animals have the same abnormal wing posture phenotype as Itp-r83Aka1091/Itp-r83Aug3 animals raised at 25'C.

Itp-r83Aka1091/Itp-r83Aug3 does not suppress the slow return to basal [Ca[2+]]i levels seen in neurons cultured from Ca-P60AKum170/+ larvae following depolarisation with 70mM KCl.

The reduced viability, abnormal wing posture, flight behaviour defects and increased spontaneous firing at NMJs seen in Itp-r83Awc703/Itp-r83Awc361; Gα49B221c/+ animals, and more severely in Itp-r83Awc703/Itp-r83Awc361; Gα49B221c/Plc21Ck31911 animals, are largely suppressed by Ca-P60AKum170/+.

comt6; Ca-P60AKum170 double mutants show an increase in strong, spontaneous DLM activity in response to restrictive temperatures that is similar to comt6 single mutants. 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.

Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Fails to complement
Comments
Images (0)
Mutant
Wild-type
Stocks (1)
Notes on Origin
Discoverer

Selected as: a dominant mutation that results in paralysis of adults within 3 minutes at 40oC.

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (10)
References (14)