Open Close
General Information
Symbol
Dmel\cpxSH1
Species
D. melanogaster
Name
FlyBase ID
FBal0241995
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Key Links
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Comment:

Approximate boundaries of a ~17 kb deletion resulting from the imprecise excision of P{SUPor-P}cpxKG03023, which removes most of cpx.

Associated Sequence Data
DNA sequence
Protein sequence
 
 
Cytology
Nature of the lesion
Statement
Reference

A 17-kb intragenic deletion within cpx that removes most of the coding region generated by imprecise excision of P{SUPor-P}cpxKG03023.

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

cpx1257/cpxSH1, but not cpxSH1/+, larvae have significantly reduced locomotion, compared to controls; transheterozygotes also have significantly reduced numbers of synaptic vesicles around motor neuron T-bars and significantly increased NMJ presynaptic active zone number, but not area, compared to controls; they have significantly increased miniature excitatory postsynaptic currents (minis) and excitatory postsynaptic current (eEPSC) amplitude and decay time constant in muscle 6, compared to controls and paired-pulse depression of eEPSCs is significantly increased, compared to controls.

cpxSH1 homozygous third instar larvae exhibit a strong reduction in evoked release (eEJC), quantal content and vesicle pool size in NMJs of ventral longitudinal m6 in abdominal segments 2 and 3 when compared to controls. The mEJC frequencies are increased in m6 of cpxSH1 heterozygotes while they are increased in both m5 and m6 of cpxSH1 homozygotes when compared to controls.

Expression of cpxC140W.UAS.7A in the cpxSH1 background leads to a reduction in the frequency of mEJCs in NMJs of ventral longitudinal m6 in abdominal segments 2 and 3 of third instar larvae when compared to controls.

cpxSH1 third instar larvae exhibit a significant increase in the mini frequency of aCC/RP2 motor neurons compared to controls.

cpxSH1/cpxSH1 homozygous larvae show significant increase in the frequency of spontaneous miniature excitatory postsynaptic currents, mESPCs at the neuromuscular junction. Their amplitude, however, cannot be reliably determined since due to the high frequency the mESPCs overlap. The amplitude and area of evoked postsynaptic currents are also abnormal and is influenced by Ca[2+] concentration: both are significantly decreased at 1 and 2 mM Ca[2+] and increased at 0.25 mM Ca[2+].

cpxSH1 mutant third instar larvae display increased frequency of mini excitatory junction potentials (~spontaneous releases) along with synaptic overgrowth (increased number of boutons) at neuromuscular junctions. cpxSH1 larvae however exhibit reduced evoked responses across a range of Ca[2+].

Rescue cpxSH1 mutant larvae expressing cpxUAS.7B (with Scer\GAL4elav-C155) display normal enhancement of the frequency of spontaneous releases (mini excitatory junction potentials) after a high-frequency stimulation, whereas no such activity-dependent enhancement is observed in cpxSH1 rescue larvae expressing either cpxS126A.UAS.7B or cpxS126D.UAS.7B. Like the controls the cpxSH1 mutants rescued with cpxUAS.7B also show significant increase in the number of boutons at 29[o]C as compared to larvae reared at 25[o]C but this temperature-induced synaptic growth is abolished in rescues with either cpxS126A.UAS.7B or cpxS126D.UAS.7B.

Mutants show an increase in the frequency of spontaneous release at the third larval instar neuromuscular junction compared to controls. EPSC amplitude is reduced compared to wild type. Synaptic depression during short and long stimulation trains is different from wild type.

cpxSH1/Df(3R)Exel6140 adults show a 77% decrease in the peak excitatory postsynaptic current (EPSC) amplitude in recordings from the dorsal longitudinal muscle neuromuscular synapse compared to controls. The waveform of the EPSC is altered, showing a slowing of the EPSC rise and decay times compared to wild type. The frequency of miniature EPSCs is increased. The same phenotypes are seen in recordings of cpxSH1/Df(3R)Exel6140 larval neuromuscular junctions.

Electrophysiological recordings at 3rd instar larval abdominal muscle 6 synapses indicate that the miniature excitatory junctional potential (mini) frequency in cpxSH1 mutants is greatly enhanced compared with wild-type. cpxSH1 mutants also exhibit reduced evoked response (EJP) amplitudes compared with controls.

The enhancement of the evoked response (EJP) caused by the expression of Scer\GAL4elav-C155>cpxΔCAAX.Scer\UAS.T:Hsap\MYC over-compensates the reduced EJP phenotype in cpxSH1 mutants.

cpxSH1 escapers are sterile and usually die within 2 weeks of eclosion.

cpxSH1 mutants show reduced evoked excitatory junction potentials (EJPs) and very high levels of spontaneous EJPs at larval neuromuscular junctions.

Most of the homozygous cpxSH1 animals die before adult eclosion. Escaper adults are infertile, show severe motor defects and lack the on- and off- transients that represents normal synaptic transmission in the visual system.

cpxSH1 mutants have profound defects in spontaneous vesicle fusion. The frequency of miniature excitatory junctional potentials (minis) is greatly enhanced at cpxSH1 mutant third-instar larval abdominal muscle 6 synapses.

In high extracellular Ca[2+], evoked responses in cpxSH1 mutants after nerve simulation are significantly reduced compared with controls, whereas in low extracellular Ca[2+] no difference is observed.

The frequency of spontaneous synaptic release in cpxSH1 mutants remains strongly elevated in 0 mM extracellular calcium.

cpxSH1 mutants show a two-fold overproliferation of boutons at each muscle examined, as well as 64% more active zones.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
NOT Enhanced by
Statement
Reference
Suppressed by
Statement
Reference
NOT suppressed by
Enhancer of
Statement
Reference
NOT Enhancer of
Statement
Reference
Suppressor of
NOT Suppressor of
Statement
Reference
Other
Phenotype Manifest In
NOT Enhanced by
Statement
Reference
Suppressed by
Statement
Reference

cpxSH1 has NMJ bouton | third instar larval stage phenotype, suppressible by witA12/wit[+]

NOT suppressed by
NOT Enhancer of
Suppressor of
NOT Suppressor of
Statement
Reference
Other
Additional Comments
Genetic Interactions
Statement
Reference

brpnude/+; cpxSH1/+ double heterozygous larvae have significantly reduced locomotion, compared to controls, unlike either heterozygote alone.

brpnude/brp69; cpx1257/cpxSH1 double mutants have suppression of the increased eEPSC amplitude and mini frequency of cpx1257/cpxSH1 mutant larval muscle 6 and enhancement of the paired-pulse depression seen in both brpnude/brp69 mutants and cpx1257/cpxSH1 mutants.

Scer\GAL4elav-C155-driven expression of cpxE34A.UAS.7A in the cpxSH1 background leads to reduced frequency of mESPCs at the larval NMJ compared to the rescue line expressing cpxUAS.7A but the amplitude as well as area of the evoked excitatory postsynaptic currents is comparable in both lines.

The synaptic overgrowth (increased number of boutons) at neuromuscular junctions observed in third instar larvae mutant for cpxSH1 can be suppressed by homozygosity of Syt4BA1 (which on its own does not lead to any elevation in synaptic growth) but this fails to suppress the increased frequency of mini excitatory junction potentials. Similarly, introducing a single copy of witA12 into the cpxSH1 mutant background also rescues the synaptic overgrowth but not the elevated minis, combination with witA12/witB11 reduces the number of NMJ boutons in cpxSH1 mutants even further, below the control levels and is comparable to that observed in witA12/witB11 mutants alone.

At the restrictive temperature, evoked release is abolished in shi1; cpxSH1 double mutant animals. The elevated miniature excitatory junctional potential frequency observed at the permissive temperature is eliminated in the double mutant.

Xenogenetic Interactions
Statement
Reference

cpxSH1 mutant larvae expressing Mmus\PrkacamC.UAS under the control of Scer\GAL4elav-C155 exhibit synaptic overgrowth (increased number of boutons) at neuromuscular junctions, similar to Mmus\PrkacamC.UAS expression alone, and this is not significantly affected by co-expression of either cpxUAS.7B or cpxS126D.UAS.7B but is significantly suppressed by cpxS126A.UAS.7B.

Expression of Mmus\Cplx4Scer\UAS.cBa under the control of Scer\GAL4elav-C155 rescues the elevation of spontaneous release and the reduction of EPSC amplitude seen at the neuromuscular junction in cpxSH1 third instar larvae.

Expression of Mmus\Cplx1Scer\UAS.cBa under the control of Scer\GAL4elav-C155 partially rescues the elevation of spontaneous release seen at the neuromuscular junction in cpxSH1 third instar larvae. The EPSC amplitude in the rescued animals is elevated compared to wild type.

Expression of Scer\GAL4elav-C155>Mmus\Cplx1Scer\UAS.T:Hsap\MYC in a cpxSH1 genetic background significantly reduces the mini frequency compared to cpxSH1 single mutants. However, mini frequencies are significantly elevated in the transgene-expressing lines compared with control. The enhancement of the evoked response (EJP) caused by the expression of Scer\GAL4elav-C155>Mmus\Cplx1Scer\UAS.T:Hsap\MYC over-compensates the reduced EJP phenotype in cpxSH1 mutants.

Expression of Scer\GAL4elav-C155>Mmus\Cplx2Scer\UAS.T:Hsap\MYC in a cpxSH1 genetic background significantly reduces the mini frequency compared to cpxSH1 single mutants. However, mini frequencies are significantly elevated in the transgene-expressing lines compared with control. The enhancement of the evoked response (EJP) caused by the expression of Scer\GAL4elav-C155>Mmus\Cplx2Scer\UAS.T:Hsap\MYC over-compensates the reduced EJP phenotype in cpxSH1 mutants.

Expression of Scer\GAL4elav-C155>Mmus\Cplx3Scer\UAS.T:Hsap\MYC in a cpxSH1 genetic background significantly reduces the mini frequency compared to cpxSH1 single mutants. However, mini frequencies are significantly elevated in the transgene-expressing lines compared with control. The enhancement of the evoked response (EJP) caused by the expression of Scer\GAL4elav-C155>Mmus\Cplx3Scer\UAS.T:Hsap\MYC over-compensates the reduced EJP phenotype in cpxSH1 mutants.

Expression of Scer\GAL4elav-C155>Mmus\Cplx4Scer\UAS.T:Hsap\MYC in a cpxSH1 genetic background significantly reduces the mini frequency compared to cpxSH1 single mutants. However, mini frequencies are significantly elevated in the transgene-expressing lines compared with control. The expression of Mmus\Cplx4Scer\UAS.T:Hsap\MYC fails to restore the reduced evoked response in cpxSH1 mutants.

The enhancement of the evoked response (EJP) caused by the expression of Scer\GAL4elav-C155>Mmus\Cplx1ΔMFKK.Scer\UAS.T:Hsap\MYC over-compensates the reduced EJP phenotype in cpxSH1 mutants.

Expression of Rnor\Cplx1Scer\UAS.cXa or Mmus\Cplx3Scer\UAS.cXa using Scer\GAL4elav-C155 rescues the lethality and sterility of cpxSH1 mutants.

Expression of Rnor\Cplx1Scer\UAS.cXa or Mmus\Cplx3Scer\UAS.cXa using Scer\GAL4elav-C155 rescues the decreased evoked excitatory junction potentials (EJPs) and partially suppresses the increased spontaneous EJPs in cpxSH1 mutants.

Complementation and Rescue Data
Comments

Scer\GAL4elav-C155-driven expression of either cpxUAS.7B or cpxS126A.UAS.7B (phosphoincompetent mutant) efficiently, if not completely, rescues the synaptic overgrowth (increased number of boutons), the increased frequency of spontaneous mini excitatory junction potentials and also suppresses the reduced amplitude of evoked responses at neuromuscular junctions (observed across a range of Ca[2+]) characteristic for cpxSH1 mutant larvae. In contrast, expression of cpxS126D.UAS.7B (phosphomimetic mutant) rescues the reduced amplitude of evoked excitatory junction potentials but the rescue of the synaptic overgrowth (increased number of boutons) and increased frequency of minis is significantly weaker compared to the one elicited by cpxUAS.7B (the wild-type version).

Expression of cpxScer\UAS.7A under the control of Scer\GAL4elav-C155 fully rescues the elevation of spontaneous release and the reduction of EPSC amplitude seen at the neuromuscular junction in cpxSH1 third instar larvae.

Expression of cpxScer\UAS.7B under the control of Scer\GAL4elav-C155 partially rescues the elevation of spontaneous release seen at the neuromuscular junction in cpxSH1 third instar larvae. The EPSC amplitude in the rescued animals is elevated compared to wild type.

Expression of cpxScer\UAS.RU.T:Avic\GFP-EGFP under the control of Scer\GAL4Appl.G1a rescues the electrophysiological defects seen at the dorsal longitudinal muscle neuromuscular synapse in cpxSH1/Df(3R)Exel6140 adults.

Transgenic expression of cpxScer\UAS.T:Hsap\MYC under the control of Scer\GAL4elav-C155 in cpxSH1 mutants significantly reduces mini frequency to near control levels.

Transgene expression of cpxScer\UAS.T:Hsap\MYC rescues the evoked response (EJP) phenotype of cpxSH1.

The enhancement of the evoked response (EJP) caused by the expression of Scer\GAL4elav-C155>cpxΔCAAX.Scer\UAS.T:Hsap\MYC over-compensates the reduced EJP phenotype in cpxSH1 mutants.

Expression of cpxScer\UAS.cXa using Scer\GAL4elav-C155 rescues the lethality and sterility of cpxSH1 mutants.

Expression of cpxScer\UAS.cXa rescues the decreased evoked excitatory junction potentials (EJPs) and the increased spontaneous EJPs in cpxSH1 mutants.

Scer\GAL4elav-C155-driven pan-neuronal expression of cpxScer\UAS.cHa rescues the reduced viability, synaptic overgrowth and abnormal synaptic transmission in the visual system of cpxSH1 mutants.

Images (0)
Mutant
Wild-type
Stocks (1)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (4)
References (14)