FB2024_03 , released June 25, 2024
Allele: Dmel\fweDB56
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General Information
Symbol
Dmel\fweDB56
Species
D. melanogaster
Name
FlyBase ID
FBal0241889
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Key Links
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Allele class
Nature of the Allele
Allele class
Progenitor genotype
Cytology
Description

Amino acid replacement: Q24term.

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

C15815990T

Amino acid change:

Q24term | fwe-PA; Q24term | fwe-PB; Q24term | fwe-PC

Reported amino acid change:

Q24term

Comment:

Nucleotide substitution inferred from reported amino acid change. Position of mutation on reference sequence inferred by FlyBase curator.

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
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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

Synaptic boutons of fweDB56/fweDB25 mutant larval neuromuscular junctions exhibit impaired Clathrin-mediated endocytosis (but not exocytosis), impaired activity-dependent bulk endocytosis, a significant decrease in bulk cisternae induction after high K[+] treatment, and a significant decrease in the number of synaptic vesicles as well as increased average vesicle size, as compared to controls, and these larvae also exhibit early larval lethality.

The NMJs of fweDB25/fweDB56 mutant larvae raised at 25[o]C have smaller and more numerous boutons compared to controls, often arrayed in bunches, and are compromised in synaptic transmission. Rearing fweDB25/fweDB56 larvae at 18°C significantly reduces synaptic bouton number and arrangement to resemble wild-type.

flowerDB56 eye somatic clone mutants are morphologically normal. However, they display impaired 'on-off' transients in electroretinograms and slightly reduced depolarizations. The synaptic patterns of R7 and R8 photoreceptor subtypes of flowerDB56 mutants and wild-type are indistinguishable. The number of synaptic vesicles is reduced in flowerDB56 mutants compared to controls. They also exhibit aberrant sizes and a varying number of capitate projections.

flowerDB56 mutants display numerous extra boutons which are often small, clustered, and flowery in nature. However, the total number of active zones and the total NMJ surface area is similar to controls.

Evoked EJPs are 0.2Hz in 0.5mm or 1.0mM amplitudes in flowerDB56 mutants are similar to controls. At 10Hz in 0.5mM '[Ca[2+]'], wild-type controls display facilitation, whereas mutants display a rundown. Post-tetanic potentiation is severely impaired in flowerDB56 mutants and the EJPs recover slowly.Increased extracellular Ca[2+] concentrations can partially rescue the endocytic defects.

There is an increase in the quantal size and a decrease in the frequency of mEJPs in flowerDB56 mutants. The junctional quantal content estimated from dividing EJP by mEJP in flowerDB56 mutants is decreased by approximately 29%. flowerDB56 mutants exhibit a 41% reduction in FM1-43 dye uptake as compared to controls.

flowerDB56 mutant boutons display a severe reduction in number of synaptic vesicles (SV). SVs are also more heterogeneous in size, and their diameter is increased when compared to control boutons. There are significantly more endocytic intermediates, such as omega structures and collared pits, after stimulation.

There is a significant decrease in resting intracellular Ca[2+] levels in flowerDB56 mutants compared to controls.

External Data
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Phenotypic Class
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement
Reference

shi1/flowerDB56 mutants are synthetic lethal.

Xenogenetic Interactions
Statement
Reference

Expression of Mmus\Cacfd1Scer\UAS.2.T:Zzzz\FLAG,T:Ivir\HA1 under the control of Scer\GAL4nSyb.PS rescues the Clathrin-mediated endocytosis defects, the activity-dependent bulk endocytosis defects, and the lowered synaptic vesicle numbers seen in larval neuromuscular junctions of fweDB25/fweDB56 mutants, and also rescues the early larval lethality observed in these mutants.

Complementation and Rescue Data
Fails to complement
Comments

Expression of fweRB.Scer\UAS.T:Ivir\HA1.T:Zzzz\FLAG under the control of Scer\GAL4nSyb.PS or Scer\GAL4elav.PU completely rescues the Clathrin-mediated endocytosis defects, and when expressed under the control of Scer\GAL4nSyb.PS, rescues the activity-dependent bulk endocytosis and lowered synaptic vesicle numbers and the increased vesicle size seen in larval neuromuscular junctions of fweDB25/fweDB56 mutants.

Expression of fweRB.E79Q.Scer\UAS.T:Ivir\HA1.T:Zzzz\FLAG under the control of Scer\GAL4nSyb.PS completely rescues the Clathrin-mediated endocytosis defects, the activity-dependent bulk endocytosis defects, the lowered synaptic vesicle numbers, and the increased vesicle size, but does not rescue the decreased bulk cisternae, seen in larval neuromuscular junctions of fweDB25/fweDB56 mutants.

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Mutant
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Stocks (1)
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Synonyms and Secondary IDs (3)
Reported As
Name Synonyms
Secondary FlyBase IDs
    References (6)