FB2024_03 , released June 25, 2024
Allele: Dmel\nwk2
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General Information
Symbol
Dmel\nwk2
Species
D. melanogaster
Name
FlyBase ID
FBal0154818
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
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Disease-implicated variant(s)
 
Phenotypic Data
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Phenotype Manifest In
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nwk2/nwk2 third instar larvae do not have significantly different miniature excitatory junction potential (mEJP) amplitude, but do have significant reduction in evoked EJP amplitude and quantal content (number of vesicles released per action potential), at the NMJ compared to controls.

nwk1/nwk2 mutant third instar larvae show an increase in the total synaptic bouton number at the neuromuscular junction as well as an increase in the satellite boutons.

The average number of boutons and of satellite boutons at the neuromuscular junction is increased in mutant larvae.

Total bouton number and satellite bouton number at the neuromuscular junction is increased in nwk1/nwk2 larvae compared to controls.

nwk2 third instar larvae display synaptic overgrowth and an increase in bouton number in segment A3, muscle 6/7 compared to wild type.

nwk1/nwk2 mutants exhibit an increase in overall bouton number.

Expression of nwkSH3ab.Scer\UAS under the control of Scer\GAL4elav-C155 enhances the synaptic overgrowth and increased bouton number phenotypes seen in nwk1/nwk2 third instar larvae.

Homozygous and hemizygous larvae show an increase in bouton number/muscle area, at the neuromuscular junction (NMJ), an increase in NMJ length/muscle area and an increase in the number of branching boutons per NMJ compared to wild type. The general anatomy of type 1b boutons at neuromuscular junction 6/7 appears normal in mutant larvae; the size and abundance of synaptic vesicles appears normal and the distribution of T bars per synaptic contact is similar to wild type. However, the general shape of the boutons is abnormal in the mutant larvae; they are elliptical in cross section (compared to circular cross-sections in wild type) and the surface area and volume of the boutons are reduced (by 42% and 60% respectively) compared to wild type. The mutant boutons have 50% fewer synaptic contacts than wild-type boutons. The mean amplitude of the excitatory junctional current (EJC) at neuromuscular junction 6/7 is reduced by more than 50% compared to wild-type larvae. The amplitude of miniature EJCs (quantal size) is slightly increased compared to wild type. mEJC frequency is not significantly different from wild type. Heterozygotes show a low incidence of hyperbranching of boutons at the larval NMJ.

External Data
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Genetic Interactions
Statement
Reference

SH3PX110A/SH3PX1C1 nwk2/nwk2 double mutants do not have significantly different quantal content deficits or further reduced evoked EJP amplitude compared to nwk2/nwk2 mutants at the third instar larval neuromuscular junction (though there is a trend towards reduced quantal content and EJP amplitude).

The increase in average bouton number and satellite bouton number at the neuromuscular junction which is seen in nwk2 larvae is suppressed if they are also carrying either Snx16Δ1/Snx16e01600 or Snx16Δ2/Snx16e01600.

The increase in average satellite bouton number at the neuromuscular junction which is seen in nwk2 larvae is suppressed if they are also carrying arrk08131/arr2.

The increase in total bouton number and satellite bouton number at the neuromuscular junction that is seen in nwk1/nwk2 larvae is enhanced if the larvae are also carrying endoAEY02730/+, Dap160Δ1/+ or shi1/+.

witA12/+ suppresses the increase in total bouton number at the neuromuscular junction that is seen in nwk1/nwk2 larvae.

Expression of tkvQ199D.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav.PU enhances the increase in the average number of satellite boutons at the neuromuscular junction that is seen in nwk2 larvae.

Cdc422 nwk2 double mutants exhibit more severe synaptic overgrowth and an increased number of boutons and satellite boutons compared to either single mutant.

Expression of Cdc42Ubi-p63E.T:Hsap\MYC rescues the synaptic overgrowth and increased bouton and satellite bouton number phenotypes seen in nwk2 Cdc422 double mutant larvae.

WASp1 nwk2 double mutant larvae display more severe neuromuscular junction (NMJ) phenotypes than either single mutant with respect to bouton number, branch formation and NMJ length. The complexity of hyperbranching at the NMJ is also dramatically increased in the double mutants.

Xenogenetic Interactions
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Complementation and Rescue Data
Fails to complement
Partially rescued by
Comments

The increased number of boutons at the neuromuscular junction observed in the nwk1/nwk2 mutant third instar larvae is rescued by expression of nwkScer\UAS.T:Avic\GFP-EGFP, is not changed by expression of nwkΔ1-428.Scer\UAS.T:Avic\GFP-EGFP and is increased further by expression of nwk1-428.Scer\UAS.T:Avic\GFP-EGFP under the control of Scer\GAL4elav-C155 in the mutant background.

Expression of nwkScer\UAS.cCa under the control of Scer\GAL4elav-C155 partially rescues the synaptic overgrowth and increased bouton number phenotypes seen in nwk1/nwk2 third instar larvae.

Expression of nwkSH3a.Scer\UAS under the control of Scer\GAL4elav-C155 fails to rescue the synaptic overgrowth and increased bouton number phenotypes in nwk1/nwk2 third instar larvae.

Expression of nwkSH3b.Scer\UAS under the control of Scer\GAL4elav-C155 fails to rescue the synaptic overgrowth and increased bouton number phenotypes seen in nwk1/nwk2 third instar larvae.

Expression of nwkSH3ab.Scer\UAS under the control of Scer\GAL4elav-C155 enhances the synaptic overgrowth and increased bouton number phenotypes seen in nwk1/nwk2 third instar larvae.

Expression of nwkΔC.Scer\UAS under the control of Scer\GAL4elav-C155 partially rescues the synaptic overgrowth and increased bouton number phenotypes seen in nwk1/nwk2 third instar larvae.

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References (10)