FB2025_01 , released February 20, 2025
Allele: Dmel\Lrrke03680
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General Information
Symbol
Dmel\Lrrke03680
Species
D. melanogaster
Name
FlyBase ID
FBal0185431
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
e03680, dLRRKe03680, LrrkP1
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Nature of the Allele
Progenitor genotype
Associated Insertion(s)
Cytology
Description
Allele components
Component
Use(s)
Inserted element
Mutations Mapped to the Genome
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 ( 1 )
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 

Dendritic phenotypes are observed when Lrrke03680 is in combination with Df(3R)del6.

Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Lrrke03680 homozygotes show an increased number of autophagosomes (Atg8a-positive puncta) in the anterior medulla.

Lrrke03680 heterozygotes exhibit a significant increase in the number of type Ib synaptic boutons at the third instar larval neuromuscular junction, as compared to wild-type controls.

Lrrke03680/+, Lrrke03680/Lrrke03680 or Lrrke03680/Lrrkex1 mutant larval neuromuscular junctions do not exhibit any significant difference in amplitude of miniature excitatory junction currents (mEJCs), EJCs, or quantal content, as compared to controls. Lrrke03680/Lrrke03680 and Lrrke03680/Lrrkex1, but not Lrrke03680/+, mutant larval neuromuscular junctions exhibit an increase in the total number of synaptic boutons, but Lrrke03680/Lrrke03680 mutants do not show a difference in the total number of presynaptic release sites per NMJ.

In Lrrke03680 homozygotes, the presynaptic region of third instar larval neuromuscular junctions fails to present the expected starvation-induced formation of autophagosomes (detected as fluorescent puncta of Atg8 or Lamp in confocal microscopy images), but presents no defects in autophagosome density under normal diet, as compared to controls; In adults reared under constant light, but not under constant dark, the eye exhibits a significant decrease in depolarization amplitude in response to light pulses (at day 3 of light exposure) and significant decreases in the rhabdomere number per ommatidium and in the photoreceptor terminal number per lamina cartridge (at day 7 of light exposure), as compared to controls;

Df(3R)del6/Lrrke03680 mutant dendritic arborizing (da) neurons contain fewer stationary golgi outposts (GOPs) than in controls, and fewer than in Df(3R)del6 heterozygotes alone. Most of the dynamic outposts move preferentially in the anterograde direction (towards dendritic ends) rather than the retrograde shift (towards cell bodies) seen in Df(3R)del6/+ alone. Displacement in the anterograde direction is significantly increased compared to controls, but in the retrograde direction is slightly but not significantly decreased. Velocity of movement is increased in both directions compared with controls. The distribution of GOPs is shifted distally compared with Df(3R)del6/+ but the number of GOPs is not significantly different.

Terminal dendrites of Df(3R)del6/Lrrke03680 mutant dendritic arborising (da) neurons show no significant difference in the displacement of extension or retraction, but are more frequent in extension and less frequent in retraction than Df(3R)del6/+ controls. Dendritic arborization is more complex than in controls, with increased terminal branches. This increase in dendrites is seen in class IV neurons, but not in class I.

The overall organization and structure of homozygous Lrrke03680 mutant flies appears normal except reduced body size, including compound eyes. There are fewer ommatidia in Lrrke03680 mutant flies compared to controls.

Lrrke03680 homozygous flies do not show premature follicle cell death.

Lrrke03680 homozygous flies show a mild increase in the size of the late endosomal compartment in a subset of cells, but no difference in lysosome morphology.

Homozygous and Lrrke03680/Df(3R)BSC141 females show a dramatic reduction in fertility compared to wild type.

The amplitude of the excitatory junctional potential (EJP) at the neuromuscular junction of mutant third instar larvae does not show a difference compared to controls at low-frequency stimulation in 2mM external calcium. However the mutants fail to maintain release during intense (10Hz) stimulation in 2mM calcium. mEJP amplitude in 0.5mM Ca[2+] is markedly increased compared to controls.

Ultrastructurally, mutant boutons stimulated using 60mM Kcl for 1 minute prior to fixation show an increased density of cisternal structures and larger vesicles at the expense of normal-sized synaptic vesicles compared to wild-type stimulated boutons.

Transheterozygous Lrrke03680/DfLrrk mutants display neuromuscular junction overgrowth and irregularly shaped boutons. These mutants exhibit a 41% increase in type I boutons compared to controls. Type Ib bouton number is not significantly changed, whereas type Is or irregularly shaped small-sized boutons are significantly increased. No significant change in muscle size is observed in these mutants. Average bouton size in Lrrke03680/DfLrrk mutants is noticeably smaller. Neuromuscular junction length and branch number in Lrrke03680/DfLrrk mutants after normalisation with muscle size are increased by 56 and 38%, respectively. Lrrke03680 homozygous mutants show similar phenotypes, although the bouton number increase is slightly less than that seen in Lrrke03680/DfLrrk mutants.

Lrrke03680 mutants exhibit a significant increase of futsch-positive MT loops, suggesting that Lrrk controls the organisation of MT cytoskeleton.

Newly synthesized tubulin inside synaptic boutons appears more elaborate and tangled in Lrrke03680 mutants.

Lrrke03680 mutants exhibit an increase in mitochondria number in terminal boutons.

Lrrke03680 mutants do not display any significant difference in mEJC amplitude compared with wild-type controls. mEJC frequency is significantly increased in Lrrke03680 mutants. Lrrke03680 heterozygous animals show a moderate increase of mEJC frequency. In terms of EJC amplitude, Lrrke03680 mutants show a significant reduction. Quantal content, a representation of synaptic junction efficacy, is also significantly reduced in Lrrke03680 mutants.

Dendrite arborization appears normal in dendritic arborization (DA) neurons of homozygous Lrrke03680 larvae.

Lrrke03680 females show a marked reduction in fertility and fecundity, both of which become severer with age. Homozygous males are fully fertile. Animals show severely impaired locomotor activity.

Dopaminergic neurons in the dorsomedial region of Lrrke03680 mutant brains display a shrunken morphology.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Enhancer of
Suppressor of
Statement
Reference

Lrrke03680 is a suppressor of abnormal flight | recessive phenotype of park25

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

Lrrke03680 has autophagosome | third instar larval stage | nutrition conditional phenotype, suppressible by EndoAS75D.CyPet

Lrrke03680 has NMJ bouton phenotype, suppressible by Thork13517

Lrrke03680 has neuromuscular junction phenotype, suppressible by futschN94/futsch[+]

Lrrke03680 has NMJ bouton phenotype, suppressible by futschN94/futsch[+]

NOT suppressed by
Statement
Reference

Lrrke03680 has autophagosome | third instar larval stage | nutrition conditional phenotype, non-suppressible by EndoAS75A.CyPet

Enhancer of
Suppressor of
Statement
Reference
NOT Suppressor of
Statement
Reference

Lrrk[+]/Lrrke03680 is a non-suppressor of wing vein | adult stage phenotype of N55e11

Other
Additional Comments
Genetic Interactions
Statement
Reference

Lrrke03680 homozygosity rescues the increased size and decreased number of synaptic vesicles in the third instar larval neuromuscular junction of Vps351/Vps35MH20 transheterozygotes does not rescue their prepupal lethality.

Lrrke03680 heterozygosity suppresses the decreased sleep bouts observed in Vps351 heterozygous adults, even leading to their significant increase as compared to controls.

Double heterozygosity for Lrrke03680 and Vps35MH20 suppresses the increased number of type Ib synaptic boutons observed in the third instar larval neuromuscular junction of Vps35MH20 or Lrrke03680 heterozygotes.

Lrrke03680/+ blocks the increased quantal content seen in larval NMJs expressing GluRIIAM614R.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4Mhc.PW, via a decrease in excitatory junction current (EJC) amplitude.

Lrrke03680/Lrrke03680 blocks the increased quantal content seen in GluRIIASP16/Df(2L)cl-h4 mutant larval NMJs, via a decrease in excitatory junction current (EJC) amplitude.

Lrrke03680/+ suppresses the increase in excitatory junction current amplitude and quantal content seen in larvae NMJs expressing TorWT.Scer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4Mhc.PW.

The failure in starvation-induced autophagosome formation observed at the presynaptic region of Lrrke03680-homozygous third instar larval neuromuscular junctions is rescued by one copy of EndoAS75D.T:Avic\GFP-CyPet, but not by one copy of EndoAS75A.T:Avic\GFP-CyPet; under normal diet conditions, however, the presence of one copy of EndoAS75D.T:Avic\GFP-CyPet leads to a significant increase in the density of autophagosomes at the same site.

The vein thickening and ectopic veins phenotype characteristic for N55e11 mutant adults is not modified by combination with a single copy of Lrrke03680.

The frequency of the vein thickening phenotype observed in Dl3 heterozygote adults is significantly increased by combination with a single copy of Lrrke03680.

The wing notching phenotype characteristic for adults expressing neurΔRING.Scer\UAS.T:Avic\GFP-EGFP under the control of Scer\GAL4dpp.PU is partially suppressed by combination with Lrrke03680 in homozygous state.

One copy of Lrrke03680 suppresses the reduction in dendritic ends seen when lvaDN.Scer\UAS is expressed in dendritic arborizing neurons under the control of Scer\GAL4109(2)80. Adding one copy of Df(3R)del6 further suppresses the phenotype.

The increased clustering of lysosomes which is seen in the follicle cells of females expressing Rab7Q67L.Scer\UAS.P\T.T:Avic\GFP-YFP under the control of Scer\GAL4CY2 is enhanced in a Lrrke03680 background.

Co-expression of foxoScer\UAS.cPa and forP1.Scer\UAS under the control of Scer\GAL4GMR.PF results in degeneration of the eye. The severity of this phenotype is not suppressed byLrrke03680/Lrrke03680.

endoAΔ4/+ suppresses the reduced excitatory junctional potential amplitude which is seen at the neuromuscular junction of Lrrke03680 third instar larvae during 10Z stimulation in 2mM calcium.

Expression of foxoScer\UAS.cKb under the control of Scer\GAL4elav.Switch.PO in a Lrrke03680/Lrrke03680 background in the presence of RU486 throughout the lifespan has no effect on lifespan.

The synaptic overgrowth phenotype seen in Lrrke03680 homozygotes is suppressed by the simultaneous loss of Thor in a homozygous Thork13517 background.

Removal of futsch activity in a heterozygous futschN94 background rescues the synaptic overgrowth phenotype found in Lrrke03680 heterozygotes.

The significant increase of futsch-positive MT loops seen in Lrrke03680 mutants is unaffected by a Thork13517 mutant background.

Lrrke03680 suppresses flight and climbing defects as well as dopaminergic PPL1 neuron loss in park25/park25 or Pink1B9/Pink1B9 flies.

Xenogenetic Interactions
Statement
Reference

The failure of Lrrke03680 homozygotes to exhibit starvation-induced formation of autophagosomes at the third instar larval neuromuscular junction presynaptic region is suppressed by the expression of Hsap\LRRK2Scer\UAS.T:SV5\V5 under the control of Scer\GAL4Toll-6-D42.

Expression of Hsap\LRRK2Scer\UAS.cLa.T:Zzzz\FLAG in dendritic arborizing neurons under the control of either Scer\GAL4109(2)80 or Scer\GAL4ppk.PU suppresses the dendrite overgrowth seen in Df(3R)del6/Lrrke03680 mutants.

Expression of Hsap\LRRK2Scer\UAS.cLa.T:Zzzz\FLAG in dendritic arborizing class IV neurons under the control of Scer\GAL4ppk.PU suppresses the preference for anterograde movement (towards dendritic ends) seen in Df(3R)del6/Lrrke03680 mutant golgi outposts (GOPs), with the resulting GOPs showing the retrograde preference (towards cell bodies) seen in the Scer\GAL4ppk.PU control.

Expression of Hsap\LRRK2Scer\UAS.cCa under the control of Scer\GAL4GMR.PU rescues the reduced eye size seen in Lrrke03680 mutant flies.

Lrrke03680/+ partially suppresses the reduction in electroretinogram amplitude seen in 28 day old flies expressing Hsap\LRRK2G2019S.Scer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4ple.PG.

Lrrke03680/+ partially suppresses the dendrite degeneration phenotype resulting from the expression of Scer\GAL4109(2)80>Avic\GFPScer\UAS.S65T.I167T.T:Btau\MAPT. Dendrites of the Avic\GFPScer\UAS.S65T.I167T.T:Btau\MAPT-expressing neurons are longer and the number of dendritic ends is increased. The suppression by Lrrke03680/+ is also observed in inclusion formation and microtubule fragmentation.

Complementation and Rescue Data
Partially rescued by

Lrrke03680 is partially rescued by LrrkTag:MYC

Comments

The failure of Lrrke03680 homozygotes to exhibit starvation-induced formation of autophagosomes at the third instar larval neuromuscular junction presynaptic region is rescued by one copy of Lrrk+tCH322-120O10.

Expression of LrrkScer\UAS.T:Avic\GFP-YFP.Venus in class IV dendritic arborizing neurons under the control of Scer\GAL4ppk.PU rescues the reduction in golgi outposts in the dendrites of Lrrke03680/Df(3R)del6 mutants. The preference for anterograde movement (towards dendritic ends) is reverted to the preference for retrograde movement (towards cell bodies) seen in Df(3R)del6/+ and the increased anterograde displacement is suppressed. The mean velocities are returned to close to control levels. The increase in dendritic arborization seen in Lrrke03680/Df(3R)del6 mutants is suppressed when LrrkScer\UAS.T:Avic\GFP-YFP.Venus is expressed in all da neurons under the control of Scer\GAL4109(2)80.

A single copy of LrrkT:Hsap\MYC partially rescues the reduced fertility of Lrrke03680 homozygous females.

Expression of LrrkScer\UAS.cDa under the control of Scer\GAL4CY2 fully rescues the reduced fertility of Lrrke03680/Df(3R)BSC141 females.

Muscle expression of LrrkScer\UAS.cIa (under the control of Scer\GAL4Mhc.PW) rescues the synaptic morphology phenotype and average bouton size found in Lrrke03680 homozygous mutants.

Neuronal expression of LrrkScer\UAS.cIa (under the control of Scer\GAL4elav-C155 results in a partial but still significant rescue of synaptic morphology and average bouton size in Lrrke03680 mutants.

Muscle or neuronal expression of Lrrk3KD.Scer\UAS (under the control of Scer\GAL4Mhc.PW or Scer\GAL4elav-C155 respectively) fails to rescue the synaptic morphology phenotype and average bouton size found in Lrrke03680 homozygous mutants.

Muscle expression of LrrkScer\UAS.cIa (through Scer\GAL4Mhc.PW) fails to rescue the alterations of mEJC frequency, EJC amplitude, or quantal content in Lrrke03680 mutants.

Neuronal expression of LrrkScer\UAS.cIa (through Scer\GAL4elav-C155) partially rescues EJC amplitude in Lrrke03680 mutants, but fails to significantly rescue quantal content.

The climbing defects of Lrrke03680 mutant animals is rescued by expression of LrrkWT.Scer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4hs.PB.

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Synonyms and Secondary IDs (14)
References (25)