Imprecise excision of the progenitor insertion, resulting in a deletion of nearly 2kb, which removes the first three exons of Vps35, including the translation start site.
abnormal gravitaxis (with Vps35E42), with Scer\GAL4da.PU, Vps35UAS.D650N
abnormal gravitaxis (with Vps35E42), with Scer\GAL4da.PU, Vps35UAS.R550W
NMJ bouton | increased number (with Vps35E42)
Vps35MH20 clones in the pupal wing present planar cell polarity defects, as shown by decreased core protein asymmetry and decreased planar polarity coordination (Pk and Fmi proteins), as well as a delay in wing trichome initiation, as compared to controls.
Vps35MH20/Vps351 transheterozygotes are lethal at the prepupal stages. Their third instar larval neuromuscular junction exhibit a significant decrease in the size of synaptic boutons and reciprocal increase in the number of type Ib boutons (despite of insignificant changes in the number of active zones per bouton), a significant decrease in the synaptic pool, associated with the reciprocal significant decrease in number and increase in size of synaptic vesicles at active zones, a significant decrease in endocytosis, associated with a significant increase in the number of endocytic intermediates per active zone, and subtle ultrastructural defects at the subsynaptic reticulum, as compared to controls; these neuromuscular junctions also exhibit neurotransmission defects, namely a significant increase in miniature excitatory junction potential amplitude, a significant decrease in quantal content under low stimulation conditions, despite of insignificant changes in both excitatory junction potential amplitude and in paired-pulse ratio, and a significant decrease in excitatory junction potential amplitude under high stimulation conditions, as compared to controls.
Vps35MH20 heterozygous third instar larvae exhibit a significant decrease in locomotor activity. Their neuromuscular junctions exhibit a significant increase in the number of type Ib synaptic boutons and a significant decrease in excitatory junction potential amplitude under high stimulation conditions, as compared to wild-type controls. Adult heterozygotes exhibit a significant decrease in lifespan, a defective sleep behavior, shown by a reciprocal significant increase in sleep bouts during the light period and a significant decrease in sleep bouts during the dark period, and a significant decrease in spontaneous synaptic activity by adult dendritic arborizing neuron, as compared to controls.
Vps35MH20 mutant third instar larvae do not show lysosomal expansion phenotype.
Vps35MH20/Vps35E42 mutants show supernumerary boutons and a dramatic reduction in larval locomotion.
Flies expressing Vps35Scer\UAS.cMa under the control of Scer\GAL4da.PU in a Vps35MH20/Vps35E42 mutant background show similar climbing ability to controls.
Flies expressing Vps35Scer\UAS.D650N under the control of Scer\GAL4da.PU in a Vps35MH20/Vps35E42 mutant background show climbing defects.
Flies expressing Vps35Scer\UAS.L800M under the control of Scer\GAL4da.PU in a Vps35MH20/Vps35E42 mutant background show similar climbing ability to controls.
Flies expressing Vps35Scer\UAS.R550W under the control of Scer\GAL4da.PU in a Vps35MH20/Vps35E42 mutant background show climbing defects.
Mutant clones of Vps35MH20 in eye discs exhibit a nearly complete loss of Vps26 signalling and a subsequent progressive loss of ERG amplitudes compared to controls and some morphological defects in aged photoreceptor cells.
Vps35MH20 flies raised in a light/dark cycle for 4 days show obvious ultrastructural defects in photoreceptor cells when compared to controls. These defects include a dramatic increase in late endosomes and lysosomes. However, photoreceptor cells in dark-reared Vps35MH20 flies do not show an increased number of late endosomes or lysosomes when compared to controls.
The follicular epithelium loses its monolayer structures and appears multilayered in 19% of homozygous follicle cell clones between stages 7 and 10 of oogenesis.
Homozygous larvae develop melanotic tumours during late larval stages and die as prepupae.
Mutant embryos derived from homozygous female germline clones die at the end of embryogenesis.
Homozygous clones in the wing result in wing notching.
Vps35MH20 has abnormal neurophysiology | third instar larval stage | dominant phenotype, enhanceable by Rab5UAS.GFP/Scer\GAL4Toll-6-D42
Vps35MH20/Vps351 has abnormal size | third instar larval stage phenotype, suppressible by Rab5UAS.GFP/Scer\GAL4da.G32
Vps35MH20/Vps351 has abnormal size | third instar larval stage phenotype, suppressible by Rab11UAS.ORF.Tag:HA/Scer\GAL4da.G32
Vps35MH20/Vps351 has abnormal size | third instar larval stage phenotype, suppressible by LrrkUAS.cIa/Scer\GAL4da.G32
Vps35MH20/Vps351 has abnormal size | third instar larval stage phenotype, suppressible by Lrrk[+]/Lrrke03680
Vps35MH20 has abnormal neuroanatomy | dominant | third instar larval stage phenotype, suppressible by Lrrk[+]/Lrrke03680
Vps35MH20 has abnormal neuroanatomy | dominant | third instar larval stage phenotype, suppressible by LrrkUAS.cIa/Scer\GAL4da.G32
Vps35MH20 has abnormal neurophysiology | dominant | third instar larval stage phenotype, suppressible by Lrrk[+]/Lrrk1
Vps35MH20 has abnormal neurophysiology | dominant | third instar larval stage phenotype, suppressible by LrrkUAS.cIa/Scer\GAL4da.G32
Vps35MH20 has abnormal neurophysiology | dominant | third instar larval stage phenotype, suppressible by Scer\GAL4Toll-6-D42/EndoAUAS.cVa
Vps35MH20 has abnormal neurophysiology | dominant | third instar larval stage phenotype, suppressible by Rab11UAS.ORF.Tag:HA/Scer\GAL4Toll-6-D42
Vps35MH20 has abnormal neurophysiology | dominant | third instar larval stage phenotype, suppressible | partially by Rab5GD10492/Scer\GAL4Toll-6-D42
Vps35MH20 has abnormal locomotor behavior | dominant | third instar larval stage phenotype, suppressible by LrrkUAS.cIa/Scer\GAL4da.G32
Vps35MH20 has abnormal locomotor behavior | dominant | third instar larval stage phenotype, suppressible by Lrrk[+]/Lrrk1
Vps35MH20 has abnormal locomotor behavior | dominant | third instar larval stage phenotype, suppressible by Rab5UAS.GFP/Scer\GAL4da.G32
Vps35MH20 has abnormal locomotor behavior | dominant | third instar larval stage phenotype, suppressible by Rab11UAS.ORF.Tag:HA/Scer\GAL4da.G32
Vps35MH20/Vps35E42 has abnormal locomotor behavior | larval stage phenotype, suppressible | partially by Scer\GAL4da.PU/Hsap\VPS35R524W.UAS
Vps35MH20/Vps35E42 has abnormal locomotor behavior | larval stage phenotype, suppressible | partially by Scer\GAL4da.PU/Hsap\VPS35L774M.UAS
Vps35MH20/Vps35E42 has abnormal locomotor behavior | larval stage phenotype, suppressible by Scer\GAL4da.PU/Hsap\VPS35UAS.cMa
Vps35MH20/Vps35E42 has abnormal locomotor behavior | larval stage phenotype, suppressible | partially by Scer\GAL4da.PU/Hsap\VPS35D620N.UAS
Vps35MH20/Vps351 has lethal - all die before end of prepupal stage phenotype, non-suppressible by Lrrke03680/Lrrke03680
Vps35MH20/Vps351 has lethal - all die before end of prepupal stage phenotype, non-suppressible by Hsap\VPS35UAS.cIa/Scer\GAL4da.G32
Vps35MH20/Vps351 has lethal - all die before end of prepupal stage phenotype, non-suppressible by Scer\GAL4da.G32/Hsap\VPS35D620N.UAS.cIa
Vps35MH20 has abnormal neurophysiology | dominant | third instar larval stage phenotype, non-suppressible by EndoAΔ4/EndoA[+]
Vps35MH20/Vps35E42 has lethal phenotype, non-suppressible by Scer\GAL4da.PU/Hsap\VPS35UAS.cMa
Vps35MH20/Vps35E42 has lethal phenotype, non-suppressible by Scer\GAL4da.PU/Hsap\VPS35D620N.UAS
Vps35MH20/Vps35E42 has lethal phenotype, non-suppressible by Scer\GAL4da.PU/Hsap\VPS35R524W.UAS
Vps35MH20/Vps35E42 has lethal phenotype, non-suppressible by Scer\GAL4da.PU/Hsap\VPS35L774M.UAS
Vps35MH20/Vps35[+] is a suppressor of abnormal neuroanatomy | dominant | third instar larval stage phenotype of Lrrke03680
Vps35MH20/Vps35[+] is a suppressor of abnormal neuroanatomy | third instar larval stage phenotype of LrrkUAS.cIa, Scer\GAL4da.G32
Vps35MH20, park[+]/park25 has abnormal oxidative stress response phenotype
Vps35MH20, park[+]/park25 has abnormal neuroanatomy | progressive phenotype
Vps35MH20, park[+]/park25 has abnormal locomotor behavior | adult stage | progressive phenotype
Hsap\VPS35UAS.cMa, Scer\GAL4da.PU, Vps35MH20/Vps35E42 has majority die during pupal stage phenotype
Vps35MH20/Vps351 has type I terminal bouton | third instar larval stage phenotype, suppressible by Rab5UAS.GFP/Scer\GAL4da.G32
Vps35MH20/Vps351 has type I terminal bouton | third instar larval stage phenotype, suppressible by Rab11UAS.ORF.Tag:HA/Scer\GAL4da.G32
Vps35MH20/Vps351 has type I terminal bouton | third instar larval stage phenotype, suppressible by LrrkUAS.cIa/Scer\GAL4da.G32
Vps35MH20/Vps351 has type I terminal bouton | third instar larval stage phenotype, suppressible by Lrrk[+]/Lrrke03680
Vps35MH20/Vps351 has synaptic vesicle | third instar larval stage phenotype, suppressible by Rab5UAS.GFP/Scer\GAL4da.G32
Vps35MH20/Vps351 has synaptic vesicle | third instar larval stage phenotype, suppressible by Rab11UAS.ORF.Tag:HA/Scer\GAL4da.G32
Vps35MH20/Vps351 has synaptic vesicle | third instar larval stage phenotype, suppressible by LrrkUAS.cIa/Scer\GAL4da.G32
Vps35MH20/Vps351 has synaptic vesicle | third instar larval stage phenotype, suppressible by Lrrk[+]/Lrrke03680
Vps35MH20 has type I bouton | third instar larval stage phenotype, suppressible by Lrrk[+]/Lrrke03680
Vps35MH20 has type I bouton | third instar larval stage phenotype, suppressible by LrrkUAS.cIa/Scer\GAL4da.G32
Vps35MH20/Vps35[+] is a suppressor of type I bouton | third instar larval stage phenotype of Lrrke03680
Vps35MH20/Vps35[+] is a suppressor of type I bouton | third instar larval stage phenotype of LrrkUAS.cIa, Scer\GAL4da.G32
Vps35MH20, park[+]/park25 has dopaminergic PPL1 neuron | progressive phenotype
The prepupal lethality of Vps35MH20/Vps351 transheterozygotes is not rescued by Lrrke03680 homozygosity.
In the third instar larval neuromuscular junctions of Vps35MH20/Vps351 transheterozygotes, their reciprocal increased size and decreased number of synaptic vesicles observed are suppressed either by Lrrke03680 heterozygosity or by the expression of Rab5Scer\UAS.T:Avic\GFP, Rab11Scer\UAS.ORF.T:Ivir\HA1 or Lrrk[Scer\UAS.cIa] under the control of Scer\GAL4da.G32; their increased number of type Ib boutons and reciprocal decreased bouton size are also suppressed by the expression of either Rab5Scer\UAS.T:Avic\GFP or Rab11Scer\UAS.ORF.T:Ivir\HA1 under the control of Scer\GAL4da.G32.
The decreased locomotor activity of Vps35MH20 heterozygous third instar larvae is suppressed either by the expression of LrrkScer\UAS.cIa, Rab5Scer\UAS.T:Avic\GFP or Rab11Scer\UAS.ORF.T:Ivir\HA1 under the control of Scer\GAL4da.G32 or by Lrrk1 heterozygosity. In the neuromuscular junction of these heterozygous larvae, the decreased excitatory junction potential amplitude under high stimulation conditions is fully suppressed by the expression of LrrkScer\UAS.cIa under the control of Scer\GAL4da.G32, by the expression of EndoAScer\UAS.cVa or Rab11Scer\UAS.ORF.T:Ivir\HA1 under the control of Scer\GAL4Toll-6-D42, or by Lrrk1 heterozygosity, is partially suppressed by the expression of Rab5GD10492 under the control of Scer\GAL4Toll-6-D42, is enhanced by the expression of Rab5Scer\UAS.T:Avic\GFP under the control of Scer\GAL4Toll-6-D42, and is unaffected by EndoAΔ4 heterozygosity.
Double heterozygosity for Vps35MH20 and Lrrke03680 or the expression of LrrkScer\UAS.cIa under the control of Scer\GAL4da.G32 in a Vps35MH20 heterozygous background suppresses the increased number of type Ib synaptic boutons observed in the third instar larval neuromuscular junction of Vps35MH20 or Lrrke03680 heterozygotes, or upon expression of LrrkScer\UAS.cIa under the control of Scer\GAL4da.G32.
Vps35MH20 park25 double heterozygotes show an age-dependent reduction in climbing ability. No phenotypes are observed in either heterozygote alone.
Vps35MH20 park25 double heterozygotes show increased sensitivity to the oxidative stressor paraquat compared with either heterozygote alone, similar to that seen in park25 homozygotes. In contrast to either heterozygote alone, progressive degeneration of the dopaminergic neurons in the PPPL cluster is also seen in Vps35MH20 park25 double heterozygotes.
Vps35MH20 Pink1B9 double heterozygotes do not exhibit climbing defects.
The prepupal lethality of Vps35MH20/Vps351 transheterozygotes is not rescued by the Scer\GAL4da.G32-driven expression of Hsap\VPS35Scer\UAS.cIa or Hsap\VPS35D620N.Scer\UAS.cIa.
Expression of Hsap\VPS35Scer\UAS.cMa under the control of Scer\GAL4da.PU at 25[o] fails to suppress the phenotypes seen in Vps35MH20/Vps35E42 mutant flies. Expressing Hsap\VPS35Scer\UAS.cMa at 29[o]C rescues mutant viability to the late pupal stage, but adults fail to eclose.
Expression of Hsap\VPS35Scer\UAS.cMa under the control of Scer\GAL4da.PU suppresses the larval locomotion defects seen in Vps35MH20/Vps35E42 mutants.
Expression of Hsap\VPS35Scer\UAS.cMa under the control of Scer\GAL4da.PU at 29[o] suppresses the NMJ phenotypes seen in Vps35MH20/Vps35E42 mutant larvae.
Expression of Hsap\VPS35D620N.Scer\UAS under the control of Scer\GAL4da.PU at 25[o] fails to suppress the phenotypes seen in Vps35MH20/Vps35E42 mutant flies. Expressing Hsap\VPS35D620N.Scer\UAS at 29[o]C rescues mutant viability to the late pupal stage, but adults fail to eclose.
Expression of Hsap\VPS35D620N.Scer\UAS under the control of Scer\GAL4da.PU at 29[o] suppresses the NMJ phenotypes seen in Vps35MH20/Vps35E42 mutant larvae.
Expression of Hsap\VPS35D620N.Scer\UAS under the control of Scer\GAL4da.PU partially suppresses the larval locomotion defects seen in Vps35MH20/Vps35E42 mutants.
Expression of Hsap\VPS35R524W.Scer\UAS under the control of Scer\GAL4da.PU at 25[o] fails to suppress the phenotypes seen in Vps35MH20/Vps35E42 mutant flies. Expressing Hsap\VPS35R524W.Scer\UAS at 29[o]C rescues mutant viability to the late pupal stage, but adults fail to eclose.
Expression of Hsap\VPS35R524W.Scer\UAS under the control of Scer\GAL4da.PU partially suppresses the larval locomotion defects seen in Vps35MH20/Vps35E42 mutants.
Expression of Hsap\VPS35R524W.Scer\UAS under the control of Scer\GAL4da.PU at 29[o] suppresses the NMJ phenotypes seen in Vps35MH20/Vps35E42 mutant larvae.
Expression of Hsap\VPS35L774M.Scer\UAS under the control of Scer\GAL4da.PU at 25[o] fails to suppress the phenotypes seen in Vps35MH20/Vps35E42 mutant flies. Expressing Hsap\VPS35L774M.Scer\UAS at 29[o]C rescues mutant viability to the late pupal stage, but adults fail to eclose.
Expression of Hsap\VPS35L774M.Scer\UAS under the control of Scer\GAL4da.PU at 29[o] suppresses the NMJ phenotypes seen in Vps35MH20/Vps35E42 mutant larvae.
Expression of Hsap\VPS35L774M.Scer\UAS under the control of Scer\GAL4da.PU partially suppresses the larval locomotion defects seen in Vps35MH20/Vps35E42 mutants.
Vps35MH20/Vps351 is rescued by Scer\GAL4da.G32/Vps35UAS.cIa
Vps35MH20/Vps35E42 is rescued by Scer\GAL4da.PU/Vps35UAS.cMa
Vps35MH20/Vps351 is partially rescued by Vps35D647N.UAS/Scer\GAL4da.G32
Vps35MH20/Vps35E42 is partially rescued by Scer\GAL4da.PU/Vps35UAS.D650N
Vps35MH20/Vps35E42 is partially rescued by Scer\GAL4da.PU/Vps35UAS.R550W
Vps35MH20/Vps35E42 is partially rescued by Vps35UAS.L800M/Scer\GAL4da.PU
The prepupal lethality of Vps35MH20/Vps351 transheterozygotes is rescued by the Scer\GAL4da.G32-driven expression of Vps35Scer\UAS.cIa, but not of Vps35D647N.Scer\UAS.
In the third instar larval neuromuscular junction of Vps35MH20/Vps351 transheterozygotes, the decreased size of synaptic boutons is rescued by the expression of either Vps35Scer\UAS.cIa or Vps35D647N.Scer\UAS under the control of Scer\GAL4da.G32; the decreased pool of synaptic vesicles, the associated reciprocal increased number and decreased size of synaptic boutons, the decreased endocytosis and the subtle ultrastructural defects of the subsynaptic reticulum are rescued by the expression of Vps35Scer\UAS.cIa, but not Vps35D647N.Scer\UAS, under the control of Scer\GAL4da.G32; the increased miniature excitatory junction potential amplitude and the decreased excitatory junction potential amplitude under high stimulation conditions are rescued by the expression of Vps35Scer\UAS.cIa, but not Vps35D647N.Scer\UAS, under the control of either Scer\GAL4da.G32, Scer\GAL4Toll-6-D42 or Scer\GAL4Mhc.PK.
The decreased adult lifespan, the decreased spontaneous synaptic activity of adult dendritic arborizing neurons and the increased number of type Ib synaptic boutons at the third instar larval neuromuscular junction observed in Vps35MH20 heterozygotes are suppressed by the expression of Vps35Scer\UAS.cIa, but not of Vps35D647N.Scer\UAS, under the control of Scer\GAL4ple.PF (driver used in the dendritic arborizing neuron activity rescue experiment) or Scer\GAL4da.G32 (driver used in the other experiments).
Expression of Vps35Scer\UAS.cMa under the control of Scer\GAL4da.PU at 25[o] fails to rescue the phenotypes seen in Vps35MH20/Vps35E42 mutant flies. Expressing Vps35Scer\UAS.cMa at 29[o]C prevents the appearance of melanotic masses and fully rescues the developmental lethality, with progeny appearing in expected proportions.
Expression of Vps35Scer\UAS.cMa under the control of Scer\GAL4da.PU at 29[o] rescues the NMJ phenotypes seen in Vps35MH20/Vps35E42 mutant larvae.
Expression of Vps35Scer\UAS.cMa under the control of Scer\GAL4da.PU rescues the larval locomotion defects seen in Vps35MH20/Vps35E42 mutants.
Expression of Vps35Scer\UAS.D650N under the control of Scer\GAL4da.PU at 25[o] fails to rescue the phenotypes seen in Vps35MH20/Vps35E42 mutant flies. Expressing Vps35Scer\UAS.D650N at 29[o]C prevents the appearance of melanotic masses and fully rescues the developmental lethality, with progeny appearing in expected proportions.
Expression of Vps35Scer\UAS.D650N under the control of Scer\GAL4da.PU partially rescues the larval locomotion defects seen in Vps35MH20/Vps35E42 mutants.
Expression of Vps35Scer\UAS.D650N under the control of Scer\GAL4da.PU at 29[o] rescues the NMJ phenotypes seen in Vps35MH20/Vps35E42 mutant larvae.
Expression of Vps35Scer\UAS.L800M under the control of Scer\GAL4da.PU at 25[o] fails to rescue the phenotypes seen in Vps35MH20/Vps35E42 mutant flies. Expressing Vps35Scer\UAS.L800M at 29[o]C prevents the appearance of melanotic masses and fully rescues the developmental lethality, with progeny appearing in expected proportions.
Expression of Vps35Scer\UAS.L800M under the control of Scer\GAL4da.PU at 29[o] rescues the NMJ phenotypes seen in Vps35MH20/Vps35E42 mutant larvae.
Expression of Vps35Scer\UAS.L800M under the control of Scer\GAL4da.PU partially rescues the larval locomotion defects seen in Vps35MH20/Vps35E42 mutants.
Expression of Vps35Scer\UAS.R550W under the control of Scer\GAL4da.PU at 25[o] fails to rescue the phenotypes seen in Vps35MH20/Vps35E42 mutant flies. Expressing Vps35Scer\UAS.R550W at 29[o]C prevents the appearance of melanotic masses and fully rescues the developmental lethality, with progeny appearing in expected proportions.
Expression of Vps35Scer\UAS.R550W under the control of Scer\GAL4da.PU at 29[o] rescues the NMJ phenotypes seen in Vps35MH20/Vps35E42 mutant larvae.
Expression of Vps35Scer\UAS.R550W under the control of Scer\GAL4da.PU partially rescues the larval locomotion defects seen in Vps35MH20/Vps35E42 mutants.