FlyBase Allele Report: Dmel\Synj[1]

General Information

Symbol

Dmel\Synj¹

Species

D. melanogaster

Name

FlyBase ID

FBal0155922

Feature type

allele

Associated gene

Dmel\Synj

Associated Insertion(s)

Carried in Construct

Key Links

Genomic Maps

JBrowse

Allele class

Mutagen

ethyl methanesulfonate

Nature of the Allele

Allele class

Mutagen

ethyl methanesulfonate

(Verstreken et al., 2003)

Progenitor genotype

Cytology

Description

Nucleotide substitution: C?T.

(Verstreken et al., 2003)

Amino acid replacement: Q460term.

(Verstreken et al., 2003)

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

2R:22,082,557..22,082,557 [+]

Nucleotide change:

C22082557T

Reported nucleotide change:

C?T

Amino acid change:

Q460term | Synj-PA; Q460term | Synj-PB; Q460term | Synj-PC

Reported amino acid change:

Q460term

(Verstreken et al., 2003)

Variant Molecular Consequences

Associated Sequence Data

DDBJ / EMBL / GenBank

DNA sequence

Protein sequence

UniProtKB/Swiss-Prot

UniProtKB/TrEMBL

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 ( 1 )

Disease

Evidence

References

model of Parkinson's disease

CEA with Synj²

(Vanhauwaert et al., 2017)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

ameliorates DOORS syndrome

modeled by sky¹, sky², sky^R79C.UAS.GFP

(Fischer et al., 2016)

Comments on Models/Modifiers Based on Experimental Evidence ( 1 )

Synj¹/+ ameliorates the disease model created by Scer\GAL4^nSyb.PU-mediated expression of sky^R79C.UAS.GFP in a sky¹/sky² background.

(Fischer et al., 2016)

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

abnormal locomotor behavior | larval stage | recessive

(Verstreken et al., 2003)

abnormal neuroanatomy | somatic clone

(Verstreken et al., 2003)

abnormal neurophysiology (with Df(2R)R1-8)

(Verstreken et al., 2003)

abnormal neurophysiology (with Synj²)

(Verstreken et al., 2003)

abnormal neurophysiology | adult stage | somatic clone

(Vanhauwaert et al., 2017)

abnormal neurophysiology | somatic clone

(Verstreken et al., 2003)

abnormal neurophysiology | third instar larval stage (with Synj²)

(Vanhauwaert et al., 2017, Geng et al., 2016)

lethal | recessive

(Verstreken et al., 2003)

lethal - all die before end of larval stage (with Synj²)

(Vanhauwaert et al., 2017)

partially lethal - majority die (with Synj²)

(Geng et al., 2016)

short lived | nutrition conditional (with Synj²), with Scer\GAL4^Toll-6-D42, Synj^RQ.UAS

(Vanhauwaert et al., 2017)

Phenotype Manifest In

autolysosome | third instar larval stage | nutrition conditional (with Synj²)

(Vanhauwaert et al., 2017)

autophagosome | third instar larval stage | conditional (with Synj²), with Scer\GAL4^Toll-6-D42, Synj^RQ.UAS

(Vanhauwaert et al., 2017)

autophagosome | third instar larval stage | nutrition conditional (with Synj²)

(Vanhauwaert et al., 2017)

autophagosome | third instar larval stage | nutrition conditional (with Synj²), with Scer\GAL4^Toll-6-D42, Synj^RQ.UAS

(Vanhauwaert et al., 2017)

neuromuscular junction | third instar larval stage

(Geng et al., 2016)

neuromuscular junction | third instar larval stage (with Synj²)

(Tsai et al., 2017, Vanhauwaert et al., 2017)

neuromuscular junction | third instar larval stage | nutrition conditional (with Synj²)

(Vanhauwaert et al., 2017)

NMJ bouton | third instar larval stage (with Synj²)

(Tsai et al., 2017)

ommatidium | adult stage (with Synj²), with Scer\GAL4^nSyb.PU, Synj^RQ.UAS

(Vanhauwaert et al., 2017)

retina | adult stage | somatic clone

(Vanhauwaert et al., 2017)

synaptic vesicle | somatic clone

(Verstreken et al., 2003)

synaptic vesicle | third instar larval stage | nutrition conditional (with Synj²)

(Vanhauwaert et al., 2017)

type I terminal bouton | third instar larval stage (with Synj²)

(Vanhauwaert et al., 2017)

vesicle | third instar larval stage (with Synj²)

(Tsai et al., 2017)

Detailed Description

Statement

Reference

Synj¹/Synj² homozygous third instar larvae exhibit a significant decrease in synaptic vesicle loading (in FM1-43 loading assay) at neuromuscular junction synaptic boutons, as compared to controls.

(Tsai et al., 2017)

Synj¹ homozygous eyes in mosaic adults exhibit a strong decrease in synaptic transmission in electroretinograms, as compared to controls.

Synj¹/Synj² transheterozygotes are lethal at the third instar larval stage; mutant third instar larval neuromuscular junctions fail to sustain neurotransmission under high stimulation conditions (assessed by the amplitude of spontaneous excitatory junctional currents), and their presynaptic regions exhibit a significant decrease in the levels of endocytosis, exhibit a significant increase in the number of satellite boutons, exhibit a failure to starvation-induce mature autophagosomes (detected as fluorescent Atg8 puncta) and autolysosomes (detected as fluorescent Lamp1 puncta), and exhibit concomitant decrease in synaptic vesicles density and increase in cisternae density at boutons under starvation conditions, as compared to controls.

Synj¹/Synj² transheterozygotes expressing Synj^RQ.Scer\UAS, but not Synj^Scer\UAS.cVa, under the control of Scer\GAL4^nSyb.PU present significant decreases in adult lifespan under starvation and significant decreases in the number of intact ommatidia upon 7 day exposure to constant light, but not to constant darkness, as compared to controls; transheterozygous third instar larval neuromuscular junctions expressing Synj^RQ.Scer\UAS, but not Synj^Scer\UAS.cVa, under the control of Scer\GAL4^Toll-6-D42 present significant decreased induction of mature autophagosomes (detected as fluorescent Atg8 puncta) in the presynaptic region in response to direct electric nerve stimulation or starvation, as compared to controls; transheterozygous third instar larval neuromuscular junctions expressing Synj^Scer\UAS.cVa also do not present neurotransmission defects, as shown by insignificant differences in the amplitude and frequency of miniature and spontaneous excitatory junctional currents under basal conditions, as compared to controls.

(Vanhauwaert et al., 2017)

Synj¹/Synj² transheterozygotes have strongly decreased viability - only about 30% of control rate of survival to third instar larval stage. The mutant larvae show defects in active synaptic vesicle endocytosis (of both the exo/endo recycling pool and the reserve vesicle pool) as well as neurotransmission defects at high stimulation frequency. The normal evoked excitatory postsynaptic potential (EPSP) amplitude is comparable to controls, however the mutant larvae display a rapid rundown of the EPSP amplitude upon a high frequency stimulation sustained for a prolonged period of time.

(Geng et al., 2016)

Neuromuscular junction overgrowth is not observed in synj¹/+ third instar larvae.

(Khuong et al., 2010)

Eggs from synj¹ germ-line clones display normal yolk granules.

(Compagnon et al., 2009)

The levels of membrane uptake (dye internalisation) in synj¹ mutant synaptic boutons in response to nerve stimulation is significantly reduced compared to controls. Increased uptake is seen when these flies are treated with chlorpromazine.

(Kasprowicz et al., 2008)

When homozygous mutant somatic clones are made in the eye, the eyes appear morphologically wild-type. Electroretinogram (ERG) recordings show a depolarisation in response to light similar to controls. However almost all of these ERGs lack on/off transients, and those that are seen are very small. These animals perform as well as control flies in phototaxis assays. Photoreceptor cells and the lamina also appear grossly normal in mutant eyes. However the synaptic vesicles appear dense and cluster in highly organised rows. Other subcellular structures do not exhibit obvious defects. Homozygous mutant, or synj¹/Df(2R)R1-8 larvae move slowly, become paralysed and die as third instar larvae or early pupae. synj¹/synj² or synj¹/Df(2R)R1-8 animals exhibit defects in endocytosis. The excitatory junctional potentials (EJPs) of mutants are not significantly different from controls. During repeated stimulation at low-frequency (1Hz) the EJP amplitude declines marginally, as do controls. At Higher-frequency stimulation (10Hz) the amplitude of the EJP declines rapidly (unlike controls) in mutants to about 25% to 30% of the original response and is then maintained for the remainder of the paradigm. Synaptic vesicles are largely depleted from the synaptic boutons from mutant terminals. ERGs starting from "lights on" performed on mutant eyes largely lack on/off transients. Very occasionally a small and delayed off transient is observed.

(Verstreken et al., 2003)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Synj¹ has abnormal neuroanatomy phenotype, enhanceable by EndoA^UAS.cVa/Scer\GAL4^ey.PH

(Verstreken et al., 2003)

Suppressed by

Statement

Reference

Synj¹ has abnormal neurophysiology phenotype, suppressible by EndoA^UAS.cVa/Scer\GAL4^ey.PH

(Verstreken et al., 2003)

Other

Statement

Reference

EndoA^EP927, Synj¹ has abnormal neuroanatomy phenotype

(Verstreken et al., 2003)

EndoA^EP927, Synj¹ has abnormal neurophysiology phenotype

(Verstreken et al., 2003)

Phenotype Manifest In

Enhanced by

Statement

Reference

Synj¹ has synaptic vesicle phenotype, enhanceable by EndoA^UAS.cVa/Scer\GAL4^ey.PH

(Verstreken et al., 2003)

Suppressor of

Statement

Reference

synj[+]/Synj¹ is a suppressor of embryonic/larval neuromuscular junction | third instar larval stage phenotype of Avic\GFP^{EGFP.UAS.Tag:PH(hPLCD1)}, Scer\GAL4^nSyb.PS

(Khuong et al., 2010)

Additional Comments

Genetic Interactions

Statement

Reference

One copy of synj¹ suppresses the neuromuscular junction overgrowth seen when Hsap\PLCD1^{PH.Scer\UAS.T:Avic\GFP-EGFP} is expressed under the control of Scer\GAL4^n-syb.PS in third instar larvae.

(Khuong et al., 2010)

The reduction in FM1-43 dye uptake that is seen in tweek¹/tweek² and tweek²/Df(2L)Exel8036 animals is partially suppressed by synj¹/+.

(Verstreken et al., 2009)

endoA¹, synj¹ transheterozygotes develop normally. However the on/off transients in electroretinogram (ERG) recordings are absent in these mutants. Mutants also phototaxis normally. Photoreceptors form normal cartridges in the lamina; however rows of densely coated vesicles accumulate in mutant photoreceptor terminals. At Higher-frequency stimulation (10Hz) the amplitude of the excitatory junctional potentials (EJPs) declines rapidly (unlike controls) in mutants to about 20% of the original response and is then maintained for the remainder of the paradigm. When endoA^Scer\UAS.cVa is overexpressed (driven by Scer\GAL4^ey.PH) in mutant animals, the ERG phenotype seen starting from "lights on" stimulation is partially rescued. The large clusters of densely coated vesicles are more apparent than in synj¹ mutants alone.

(Verstreken et al., 2003)

Xenogenetic Interactions

Statement

Reference

Complementation and Rescue Data

Rescued by

Synj¹ is rescued by Scer\GAL4^nSyb.PU/Synj^UAS.cVa

(Vanhauwaert et al., 2017)

Synj¹ is rescued by Scer\GAL4^nSyb.PU/Synj^RQ.UAS

(Vanhauwaert et al., 2017)

Synj²/Synj¹ is rescued by Scer\GAL4^nSyb.PU/Synj^UAS.cVa

(Vanhauwaert et al., 2017)

Synj²/Synj¹ is rescued by Scer\GAL4^Toll-6-D42/Synj^UAS.cVa

(Vanhauwaert et al., 2017)

Synj²/Synj¹ is rescued by Synj^UAS.Tag:HA/Scer\GAL4^nSyb.PS

(Geng et al., 2016)

Synj²/Synj¹ is rescued by Synj^{S1029E.UAS.Tag:HA}/Scer\GAL4^nSyb.PS

(Geng et al., 2016)

Synj¹ is rescued by Synj^{+tCH322-188H18}

(Venken et al., 2009)

Synj¹ is rescued by Synj^+tKa

(Verstreken et al., 2003)

Partially rescued by

Synj²/Synj¹ is partially rescued by Synj^RQ.UAS/Scer\GAL4^Toll-6-D42

(Vanhauwaert et al., 2017)

Synj²/Synj¹ is partially rescued by Scer\GAL4^nSyb.PU/Synj^RQ.UAS

(Vanhauwaert et al., 2017)

Synj²/Synj¹ is partially rescued by Synj^{S1029A.UAS.Tag:HA}/Scer\GAL4^nSyb.PS

(Geng et al., 2016)

Not rescued by

Synj²/Synj¹ is not rescued by Synj^CS.UAS/Scer\GAL4^Toll-6-D42

(Vanhauwaert et al., 2017)

Comments

The defects observed at the third instar larval neuromuscular junction of Synj¹/Synj² transheterozygotes are fully and partially suppressed by the expression of Synj^Scer\UAS.cVa and Synj^RQ.Scer\UAS, respectively, under the control of Scer\GAL4^Toll-6-D42, since both expressions suppress the presynaptic increase in the number of satellite boutons, decrease in endocytosis levels, decrease in synaptic vesicle density under starvation conditions and the failure to sustain neurotransmission under high stimulation conditions, but only the expression of Synj^Scer\UAS.cVa suppresses the failure to starvation-induce presynaptic mature autophagosomes (detected as fluorescent Atg8 puncta) and autolysosomes (detected as fluorescent Lamp1 puncta) and the increase in presynaptic cisternae density under starvation conditions.

(Vanhauwaert et al., 2017)

Expression of either Synj^{Scer\UAS.T:Ivir\HA1} or Synj^{S1029E.Scer\UAS.T:Ivir\HA1} under the Scer\GAL4^nSyb.PS driver rescues the active synaptic vesicle endocytosis defects as well as the abnormal rapid rundown of evoked excitatory postsynaptic potential amplitude observed in the Synj¹/Synj² mutant larvae upon high frequency stimulation for a prolonged period of time. Expression of Synj^{S1029A.Scer\UAS.T:Ivir\HA1} fails to rescue the vesicle endocytosis defects but it does restore normal of the postsynaptic potential amplitude.

(Geng et al., 2016)

Images (0)

Mutant

Wild-type

Stocks (1)

Bloomington

24883

y^d2 w¹¹¹⁸ P{ey-FLP.N}2 P{5xglBS-lacZ.38-1}TPN1; P{neoFRT}42D Synj¹/CyO, P{GAL4-Kr.C}DC3, P{UAS-GFP.S65T}DC7

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (3)

Reported As

Symbol Synonym

2R11¹

(Verstreken et al., 2003)

Synj¹

(Inoshita et al., 2022)

synj¹

(Peng et al., 2021, Li et al., 2020, Vanhauwaert et al., 2017, Fischer et al., 2016, Geng et al., 2016, Chen et al., 2014, Khuong et al., 2010, Compagnon et al., 2009, Venken et al., 2009, Verstreken et al., 2009, Kasprowicz et al., 2008)

Name Synonyms

Secondary FlyBase IDs

References (14)

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