FlyBase Allele Report: Hsap\LRRK2[G2019S.UAS.cLa.Tag:FLAG]

General Information

Symbol

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}

Species

H. sapiens

Name

FlyBase ID

FBal0284313

Feature type

allele

Associated gene

Hsap\LRRK2

Associated Insertion(s)

Carried in Construct

P{UAS-LRRK2.G2019S.FLAG.L}

Also Known As

UAS-LRRK2-G2019S, G2019S

Key Links

Transgenic product class

missense_variant

(Lin et al., 2010)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Lin et al., 2010)

Mutagen

in vitro construct

(Lin et al., 2010)

Progenitor genotype

Carried in construct

P{UAS-LRRK2.G2019S.FLAG.L}

Cytology

Description

UASt regulatory sequences drive expression of Hsap\LRRK2 carrying amino acid substitution G2019S tagged with Tag:FLAG at the N-terminus.

(Lin et al., 2010)

Allele components

Component

Use(s)

Regulatory region(s)

UASt

binary expression system - regulatory region

Encoded product / tool

Hsap\LRRK2

Tagged with

Tag:FLAG

epitope tag

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

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

(Cording et al., 2017, Lin et al., 2015, Martin et al., 2014, Hindle et al., 2013, Lin et al., 2010)

model of Parkinson's disease 8

CEA

(Hsieh et al., 2016)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of Parkinson's disease

is ameliorated by Hsap\RPS15^T136A.UAS

(Martin et al., 2014)

is ameliorated by tau^VDRC.cUa

(Lin et al., 2010)

is ameliorated by sgg^unspecified

(Lin et al., 2010)

is ameliorated by Hsap\MAPT^T212A.UAS

(Lin et al., 2010)

is ameliorated by sgg^A81T.UAS

(Lin et al., 2010)

model of Parkinson's disease 8

is ameliorated by Miro^KK102189

(Hsieh et al., 2016)

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

Expression of the G2019S form of Hsap\LRRK2 (the most common Parkinson's disease-related mutation in humans) in dopaminergic neurons in flies results in functional and anatomical loss of visual response, providing a tractable model of visual problems which are a symptom of Parkinson's disease.

(Hindle et al., 2013)

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Lin et al., 2010)

LRRK2:p.Gly2019Ser

(FlyBase curators, 2019-)

Variants Synonym(s)

Associated human disease model(s)

Parkinson disease 8

External database links

ClinVar: LRRK2_1940

Comments concerning this variant

Phenotypic Data

Phenotypic Class

abnormal feeding behavior | adult stage, with Scer\GAL4^ple.PF

(Cording et al., 2017)

abnormal feeding behavior | adult stage, with Scer\GAL4^ple.TH-C'

(Cording et al., 2017)

abnormal feeding behavior | adult stage, with Scer\GAL4^ple.TH-D'

(Cording et al., 2017)

abnormal locomotor behavior | progressive, with Scer\GAL4^Ddc.PL

(Lin et al., 2010)

abnormal neuroanatomy, with Scer\GAL4^Ddc.PL

(Lin et al., 2010)

abnormal neuroanatomy | progressive, with Scer\GAL4^Ddc.PL

(Martin et al., 2014)

abnormal neuroanatomy | third instar larval stage, with Scer\GAL4^109(2)80

(Lin et al., 2010)

abnormal neuroanatomy | third instar larval stage, with Scer\GAL4^ppk.PG

(Lin et al., 2010)

abnormal neuroanatomy | third instar larval stage | heat sensitive, with Scer\GAL4^109(2)80, Scer\GAL80^ts.αTub84B

(Lin et al., 2010)

abnormal neurophysiology | progressive, with Scer\GAL4^ple.PF

(Hindle et al., 2013)

short lived, with Scer\GAL4^ple.PF

(Cording et al., 2017)

short lived | progressive, with Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Phenotype Manifest In

axon | progressive, with Scer\GAL4^Ddc.PL

(Lin et al., 2010)

dendrite, with Scer\GAL4^Ddc.PL

(Lin et al., 2010)

dendrite, with Scer\GAL4^ppk.PU

(Lin et al., 2015)

dendrite | third instar larval stage, with Scer\GAL4^109(2)80

(Lin et al., 2010)

dendrite | third instar larval stage, with Scer\GAL4^ppk.PG

(Lin et al., 2010)

dendritic arborizing neuron, with Scer\GAL4^ppk.PU

(Lin et al., 2015)

dendritic arborizing neuron | third instar larval stage, with Scer\GAL4^109(2)80

(Lin et al., 2010)

dendritic arborizing neuron | third instar larval stage | heat sensitive, with Scer\GAL4^109(2)80, Scer\GAL80^ts.αTub84B

(Lin et al., 2010)

dopaminergic neuron, with Scer\GAL4^Ddc.PL

(Lin et al., 2010)

dorso-lateral dopaminergic neuron, with Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Golgi stack, with Scer\GAL4^ppk.PU

(Lin et al., 2015)

larval multidendritic class IV neuron | third instar larval stage, with Scer\GAL4^ppk.PG

(Lin et al., 2010)

microtubule, with Scer\GAL4^ppk.PG

(Lin et al., 2010)

neuron | progressive, with Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Detailed Description

Statement

Reference

The expression of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} under the control of Scer\GAL4^ple.PF, Scer\GAL4^ple.TH-C' or Scer\GAL4^ple.TH-D', but not if under the control of Scer\GAL4^nSyb.PG, Scer\GAL4^Gr5a.8.5, Scer\GAL4^E49, Scer\GAL4^Ddc.PL or Scer\GAL4^Ddc.HL9, leads to a significant decrease in proboscis extension reflex (in starved flies exposed to a moderate sugar stimulus) in 3 to 18 days old adults, as compared to controls; these flies exhibit a significantly slower proboscis extension speed due to extra path, as compared to controls. In ad libitum conditions, Scer\GAL4^ple.PF-driven expression leads to a significant decrease in lifespan, as compared to controls.

(Cording et al., 2017)

As in controls, the dynamic golgi outposts (GOPs) in the dendrites of dendritic arborizing neurons expressing Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} under the control of Scer\GAL4^ppk.PU show an overall preference for retrograde movement (towards cell bodies), but show increased retrograde displacement. The displacement of GOPs moving in the anterograde direction (towards dendritic ends) is also increased compared with controls. Velocity of movement is increased in both directions compared with controls, but is more prominent in the retrograde direction.

(Lin et al., 2015)

Expression of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} under the control of Scer\GAL4^Ddc.PL results in accelerated age-dependent decline in locomotor function and a selective loss of dopamine neurons.

Expression of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} under the control of Scer\GAL4^Ddc.PL results in an elevation of bulk protein synthesis. This is prevented through the addition of the protein synthesis inhibitor anisomycin to food through adulthood. This also prevents the neurodegenerative phenotype.

Supplementing food with 10υM 4EGI-1 throughout adulthood partially rescues the locomotor deficits and loss of dopamine neurons associated with Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} expression.

(Martin et al., 2014)

28 day old flies expressing Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} under the control of Scer\GAL4^ple.PG show a significant reduction in electroretinogram amplitude compared to 3 day old flies.

(Hindle et al., 2013)

Expression of Hsap\LRRK2^{G2019S.Scer\UAS.T:Zzzz\FLAG} in dendritic arborization (DA) neurons using Scer\GAL4^109(2)80 engenders dendrite arborization defects as shown by the quantification of numbers of dendritic ends in the dorsal field of A6 segments in third instar larvae. In Hsap\LRRK2^{G2019S.Scer\UAS.T:Zzzz\FLAG}-expressing DA neurons, the dendritic field is significantly reduced. The lengths of both lower- and higher-order branches are shortened, and many terminal arbors fail to reach the segmental and dorsal-midline boundaries.

Axonal terminals of class IV dendritic arborizing neurons expressing Scer\GAL4^ppk.PG>Hsap\LRRK2^{G2019S.Scer\UAS.T:Zzzz\FLAG} remain normal, targeting to the ventral nerve cord, although the complexity of dendrites is severely compromised, displaying shorter and fewer terminal arbors and leaving some receptive fields uncovered.

When larvae carrying Scer\GAL4^109(2)80 and Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} are continuously reared at 25[o]C without temperature shift, the numbers of dendritic ends are comparable between Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} and control larvae at day 4 or day 6. When Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} larvae are shifted to 30[o]C at day 3, the DA dendrites grow normally when examined at day 4, compared to controls, indicating that Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} affects little, if any, dendrite growth in early stages of larval development. Strikingly, Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} DA neurons display a sparse dendrite pattern at day 6; the number of dendritic ends is significantly lower than that of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} DA neurons at day 4 and that of controls at day 6. Therefore, after Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} expression, the dendrite complexity is reduced in later larval stages compared with that in early stages, an indication of degeneration.

Using Scer\GAL4^Ddc.PL to drive Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} expression in dopaminergic neurons, locomotion of adult flies is affected by the third week after eclosion, and the viability shows significant decline at the fourth week compared with controls. Fly brains expressing Scer\GAL4^Ddc.PL>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} show a significant loss of dopaminergic neurons in both dorsomedial and dorsolateral groups at the fourth week after eclosion compared with controls of the same age.

Serotonin neurons appear normal in the brains of flies expressing Scer\GAL4^Ddc.PL>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG}.

Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} expression under the control of Scer\GAL4^Ddc.PL results in significant reduction of dendritic structures in two- and four-week-old adult brains. Dendrite degeneration appears to precede axon degeneration and cell-body loss in neurons expressing Scer\GAL4^Ddc.PL>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG}.

Expression of Scer\GAL4^ppk.PG>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} engenders microtubule structure defects in dendrites.

(Lin et al., 2010)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has abnormal neuroanatomy | third instar larval stage phenotype, enhanceable by Avic\GFP^{UAS.S65T.I167T.Tag:MT(btau)}, Scer\GAL4^109(2)80

(Lin et al., 2010)

NOT Enhanced by

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^Ddc.PL has abnormal neuroanatomy phenotype, non-enhanceable by sgg^UAS.cBa, Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Suppressed by

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^GMR.PU, grim^GMR.PU has visible phenotype, suppressible by Akt^{T342D.S505D.GMR}

(Chuang et al., 2014)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^Ddc.PL has abnormal neuroanatomy | progressive phenotype, suppressible by Hsap\RPS15^T136A.UAS, Scer\GAL4^Ddc.PL

(Martin et al., 2014)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has abnormal neuroanatomy | third instar larval stage phenotype, suppressible | partially by tau^VDRC.cUa, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has abnormal neuroanatomy | third instar larval stage phenotype, suppressible by Hsap\MAPT^T212A.UAS, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has abnormal neuroanatomy | third instar larval stage phenotype, suppressible | partially by sgg^unspecified/sgg[+]

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^ppk.PG has abnormal neuroanatomy | third instar larval stage phenotype, suppressible by sgg^A81T.UAS, Scer\GAL4^ppk.PG

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^Ddc.PL has abnormal neuroanatomy phenotype, suppressible by sgg^A81T.UAS, Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^Ddc.PL has abnormal locomotor behavior | progressive phenotype, suppressible by sgg^A81T.UAS, Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^Ddc.PL has short lived | progressive phenotype, suppressible by sgg^A81T.UAS, Scer\GAL4^Ddc.PL

(Lin et al., 2010)

NOT suppressed by

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^ppk.PG has abnormal neuroanatomy | third instar larval stage phenotype, non-suppressible by sgg^UAS.cBa, Scer\GAL4^ppk.PG

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^Ddc.PL has abnormal neuroanatomy phenotype, non-suppressible by sgg^UAS.cBa, Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Enhancer of

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is an enhancer of abnormal neuroanatomy | third instar larval stage phenotype of Hsap\MAPT^UAS.cWa, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is an enhancer of abnormal neuroanatomy | third instar larval stage phenotype of Hsap\MAPT^{T175A.T181A.UAS}, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is an enhancer of abnormal neuroanatomy | third instar larval stage phenotype of Hsap\MAPT^S214A.UAS, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^ppk.PG is an enhancer of abnormal neuroanatomy | third instar larval stage phenotype of Avic\GFP^{UAS.S65T.I167T.Tag:MT(btau)}, Scer\GAL4^ppk.PG

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is an enhancer of abnormal neuroanatomy | third instar larval stage phenotype of Avic\GFP^{UAS.S65T.I167T.Tag:MT(btau)}, Scer\GAL4^109(2)80

(Lin et al., 2010)

NOT Enhancer of

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is a non-enhancer of abnormal neuroanatomy | third instar larval stage phenotype of Scer\GAL4^109(2)80, sgg^A81T.UAS

(Lin et al., 2010)

NOT Suppressor of

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}/Scer\GAL4^GMR.PU is a non-suppressor of visible phenotype of grim^GMR.PU

(Chuang et al., 2014)

Phenotype Manifest In

Enhanced by

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has dendritic arborizing neuron | third instar larval stage phenotype, enhanceable by Avic\GFP^{UAS.S65T.I167T.Tag:MT(btau)}, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has dendrite | third instar larval stage phenotype, enhanceable by Avic\GFP^{UAS.S65T.I167T.Tag:MT(btau)}, Scer\GAL4^109(2)80

(Lin et al., 2010)

NOT Enhanced by

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^Ddc.PL has dendrite phenotype, non-enhanceable by sgg^UAS.cBa, Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Suppressed by

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^GMR.PU, grim^GMR.PU has eye phenotype, suppressible by Akt^{T342D.S505D.GMR}

(Chuang et al., 2014)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^GMR.PU, grim^GMR.PU has ommatidium phenotype, suppressible by Akt^{T342D.S505D.GMR}

(Chuang et al., 2014)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has dendritic arborizing neuron | third instar larval stage phenotype, suppressible by Hsap\MAPT^T212A.UAS, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has dendritic arborizing neuron | third instar larval stage phenotype, suppressible | partially by sgg^unspecified/sgg[+]

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^ppk.PG has microtubule phenotype, suppressible by sgg^A81T.UAS, Scer\GAL4^ppk.PG

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^ppk.PG has dendrite | third instar larval stage phenotype, suppressible by sgg^A81T.UAS, Scer\GAL4^ppk.PG

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^Ddc.PL has dendrite phenotype, suppressible by sgg^A81T.UAS, Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has dendritic arborizing neuron | third instar larval stage phenotype, suppressible | partially by tau^VDRC.cUa, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 has dendrite | third instar larval stage phenotype, suppressible | partially by tau^VDRC.cUa, Scer\GAL4^109(2)80

(Lin et al., 2010)

NOT suppressed by

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^ppk.PG has microtubule phenotype, non-suppressible by sgg^UAS.cBa, Scer\GAL4^ppk.PG

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^ppk.PG has dendrite | third instar larval stage phenotype, non-suppressible by sgg^UAS.cBa, Scer\GAL4^ppk.PG

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^Ddc.PL has dendrite phenotype, non-suppressible by sgg^UAS.cBa, Scer\GAL4^Ddc.PL

(Lin et al., 2010)

Enhancer of

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is an enhancer of dendritic arborizing neuron | third instar larval stage phenotype of Hsap\MAPT^UAS.cWa, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is an enhancer of dendritic arborizing neuron | third instar larval stage phenotype of Hsap\MAPT^{T175A.T181A.UAS}, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is an enhancer of dendritic arborizing neuron | third instar larval stage phenotype of Hsap\MAPT^S214A.UAS, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^ppk.PG is an enhancer of microtubule phenotype of Avic\GFP^{UAS.S65T.I167T.Tag:MT(btau)}, Scer\GAL4^ppk.PG

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^ppk.PG is an enhancer of dendrite | third instar larval stage phenotype of Avic\GFP^{UAS.S65T.I167T.Tag:MT(btau)}, Scer\GAL4^ppk.PG

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is an enhancer of dendritic arborizing neuron | third instar larval stage phenotype of Avic\GFP^{UAS.S65T.I167T.Tag:MT(btau)}, Scer\GAL4^109(2)80

(Lin et al., 2010)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is an enhancer of dendrite | third instar larval stage phenotype of Avic\GFP^{UAS.S65T.I167T.Tag:MT(btau)}, Scer\GAL4^109(2)80

(Lin et al., 2010)

NOT Enhancer of

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}, Scer\GAL4^109(2)80 is a non-enhancer of dendritic arborizing neuron | third instar larval stage phenotype of Scer\GAL4^109(2)80, sgg^A81T.UAS

(Lin et al., 2010)

NOT Suppressor of

Statement

Reference

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}/Scer\GAL4^GMR.PU is a non-suppressor of eye phenotype of grim^GMR.PU

(Chuang et al., 2014)

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}/Scer\GAL4^GMR.PU is a non-suppressor of ommatidium phenotype of grim^GMR.PU

(Chuang et al., 2014)

Additional Comments

Genetic Interactions

Statement

Reference

Expression of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} under the control of Scer\GAL4^GMR.PU does not significantly suppress the eye phenotypes seen upon expression of grim^GMR.PU.

(Chuang et al., 2014)

Xenogenetic Interactions

Statement

Reference

Co-expression of Hsap\RPS15^{T136A.Scer\UAS} prevents the neurodegenerative phenotype seen in flies expressing Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} under the control of Scer\GAL4^Ddc.PL.

Co-expression of Hsap\RPS15^{T136A.Scer\UAS} suppresses the elevation in bulk protein synthesis seen in flies expressiing Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} under the control of Scer\GAL4^Ddc.PL.

(Martin et al., 2014)

Co-expression of tau^VDRC.cUa alleviates the dendritic defects caused by Scer\GAL4^109(2)80>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG}. The dorsal dendritic field is almost fully restored and the number of dendritic ends is also markedly increased.

Co-expression of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} strongly enhances the dendrite defects caused by Scer\GAL4^109(2)80>Avic\GFP^{Scer\UAS.S65T.I167T.T:Btau\MAPT}. In severe cases, only six of the eight dendritic arborization (DA) neuron somas are present in the dorsal field, an indication of neuronal loss that is not detected when Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} or Avic\GFP^{Scer\UAS.S65T.I167T.T:Btau\MAPT} is expressed alone.

Co-expression of Avic\GFP^{Scer\UAS.S65T.I167T.T:Btau\MAPT} and Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} under the control of Scer\GAL4^ppk.PG causes severe microtubule destruction in dendrites.

Co-expression of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} enhances the formation of spheroid inclusions caused by Scer\GAL4^ppk.PG>Avic\GFP^{Scer\UAS.S65T.I167T.T:Btau\MAPT}-expression. The spheroid inclusions appear much more frequent in both distal and proximal dendrites when Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} is also expressed.

When co-expressed in dendritic arborization (DA) neurons, Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} causes further dendrite degeneration in DA neurons that express Hsap\MAPT^Scer\UAS.cWa.

When co-expressed in dendritic arborization (DA) neurons, Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} causes further dendrite degeneration in DA neurons that express Hsap\MAPT^{T175A.T181A.Scer\UAS}.

When co-expressed in dendritic arborization (DA) neurons, Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} causes further dendrite degeneration in DA neurons that express Hsap\MAPT^{S214A.Scer\UAS}.

When co-expressed in dendritic arborization (DA) neurons, Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} fails to cause dendrite degeneration in DA neurons that express Hsap\MAPT^{T212A.Scer\UAS}, suggesting that Hsap\MAPT^{T212A.Scer\UAS} blocks the neuronal toxicity of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG}.

Arborization is significantly restored in dendritic arborization (DA) neurons expressing Scer\GAL4^109(2)80>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} in a heterozygous sgg^unspecified genetic background.

The dendritic defects caused by Scer\GAL4^109(2)80>sgg^{A81T.Scer\UAS}-expression are not enhanced by the co-expression of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG}.

sgg^{A81T.Scer\UAS} suppresses the toxic effects of Scer\GAL4^ppk.PG>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} on microtubule fragmentation in dendritic processes.

sgg^Scer\UAS.cBa fails to suppress the toxic effects of Scer\GAL4^ppk.PG>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} on microtubule fragmentation in dendritic processes.

Co-expression of sgg^Scer\UAS.cBa in Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG}-expressing neurons by Scer\GAL4^Ddc.PL maintains the disrupted dendritic structure in 2-week-old adult brains, similar to expression of Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG} alone.

Co-expression of sgg^{A81T.Scer\UAS} restores dendritic patterns caused by Scer\GAL4^Ddc.PL>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG}. In addition, sgg^{A81T.Scer\UAS} suppresses the life-span and locomotion defects caused by Scer\GAL4^Ddc.PL>Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG}.

(Lin et al., 2010)

Complementation and Rescue Data

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Bloomington

602459

y¹ w^*; P{UAS-LRRK2.G2019S.FLAG.L}3

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Reported As

Symbol Synonym

Hsap\LRRK2^{G2019S.Scer\UAS.cLa.T:Zzzz\FLAG}

Hsap\LRRK2^{G2019S.UAS.cLa.Tag:FLAG}

LRRK2^G2019S

(Hsieh et al., 2019)

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