Loss of spastic paraplegia gene atlastin induces age-dependent death of dopaminergic neurons in Drosophila

Lee, Youngseok; Paik, Donggi; Bang, Sunhoe; Kang, Jongkyun; Chun, Bumkoo; Lee, Seungbok; Bae, Eun-Kyung; Chung, Jongkyung; Kim, Jaeseob

doi:10.1016/j.neurobiolaging.2006.09.004

Cited by 36 publications

(37 citation statements)

References 36 publications

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“…It is unlikely that these locomotor deficits result directly from the deficits in larval synaptic transmission that we have documented. Rather, these locomotor deficits might reflect agedependent degeneration of specific populations of neurons as has been reported previously for an atl hypomorph (Lee et al, 2008).…”

Section: Neuronal Loss Of Atl and Rtnl1 Causes Axon Terminal Overgrowthsupporting

confidence: 51%

“…Drosophila mutant for any of several HSP orthologs, including spartin, spastin, atl and Rtnl1, as well as spinster, exhibit similar agedependent locomotor deficits or lifespan deficits (Dermaut et al, 2005;Lee et al, 2008;Nahm et al, 2013;O'Sullivan et al, 2012;Orso et al, 2009;Sweeney and Davis, 2002). Here, we show locomotor impairment in adults with neuronal-specific atl knockdown.…”

Section: Rtnl1 Affects Evoked Neurotransmitter Release From Multiple mentioning

confidence: 54%

“…Drosophila mutant for any of several HSP orthologues similarly display behavioral deficits (Lee et al, 2008;Nahm et al, 2013;Sherwood et al, 2004). We used two assays to determine whether pan-neuronal atl inhibition generated locomotor deficits.…”

Section: Neuronal Loss Of Atl and Rtnl1 Causes Axon Terminal Overgrowthmentioning

confidence: 99%

“…These shared phenotypes might reflect disruption of a common pathway in endocytic receptor trafficking in these mutants. Some of these phenotypes, such as stabilized microtubules, agedependent locomotor deficits and increased synaptic bouton number, are also observed in flies lacking atlastin (atl) (Lee et al, 2009(Lee et al, , 2008.…”

Section: Introductionmentioning

confidence: 99%

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The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

Summerville

Faust

Fan

et al. 2016

Journal of Cell Science

108

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Hereditary spastic paraplegia (HSP) is a set of genetic diseases caused by mutations in one of 72 genes that results in age-dependent corticospinal axon degeneration accompanied by spasticity and paralysis. Two genes implicated in HSPs encode proteins that regulate endoplasmic reticulum (ER) morphology. Atlastin 1 (ATL1, also known as SPG3A) encodes an ER membrane fusion GTPase and reticulon 2 (RTN2, also known as SPG12) helps shape ER tube formation. Here, we use a new fluorescent ER marker to show that the ER within wild-type Drosophila motor nerve terminals forms a network of tubules that is fragmented and made diffuse upon loss of the atlastin 1 ortholog atl. atl or Rtnl1 loss decreases evoked transmitter release and increases arborization. Similar to other HSP proteins, Atl inhibits bone morphogenetic protein (BMP) signaling, and loss of atl causes age-dependent locomotor deficits in adults. These results demonstrate a crucial role for ER in neuronal function, and identify mechanistic links between ER morphology, neuronal function, BMP signaling and adult behavior.

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Section: Neuronal Loss Of Atl and Rtnl1 Causes Axon Terminal Overgrowthsupporting

confidence: 51%

Section: Rtnl1 Affects Evoked Neurotransmitter Release From Multiple mentioning

confidence: 54%

Section: Neuronal Loss Of Atl and Rtnl1 Causes Axon Terminal Overgrowthmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

Summerville

Faust

Fan

et al. 2016

Journal of Cell Science

108

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“…It is also worth noting that human diseases can be modeled in Drosophila by either targeting the gene of interest or by overexpressing disease causing human orthologs: the list includes Parkinson's disease, Alzheimer's disease, spinocerebellar ataxia 2 and 3 [84][85][86][87] (also https://bdsc.indiana.edu/stocks/hd/index.html). For example, overexpression in flies of human α-synuclein (the first gene discovered to be linked to familial Parkinson disease [88]) results in age-dependent loss of dopaminergic neurons and impaired locomotor activities [89].…”

Section: The Dopaminergic Systemmentioning

confidence: 99%

Big Lessons from Tiny Flies:<em> Drosophila Melanogaster </em>as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems

Kasture

Hummel

Sučić

et al. 2018

Preprint

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The brain of Drosophila melanogaster is comprised of some 100,00 neurons, 127 and 80 of which are dopaminergic and serotonergic, respectively. Their activity regulates behavioral functions equivalent to those in mammals, e.g. motor activity, reward and aversion, memory formation, feeding, sexual appetite etc. Mammalian dopaminergic and serotonergic neurons are known to be heterogeneous. They differ in their projections and in their gene expression profile. A sophisticated genetic tool box is available, which allows for targeting virtually any gene with amazing precision in Drosophila melanogaster. Similarly, Drosophila genes can be replaced by their human orthologs including disease-associated alleles. Finally, genetic manipulation can be restricted to single fly neurons. This has allowed for addressing the role of individual neurons in circuits, which determine attraction and aversion, sleep and arousal, odor preference etc. Flies harboring mutated human orthologs provide models, which can be interrogated to understand the effect of the mutant protein on cell fate and neuronal connectivity. These models are also useful for proof-of-concept studies to examine the corrective action of therapeutic strategies. Finally, experiments in Drosophila can be readily scaled up to an extent, which allows for drug screening with reasonably high throughput.

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Modeling Hereditary Spastic Paraplegias in Fruit Flies: Potential of Its Genetic Paraphernalia

Bhat

Kumar

2019

Insights Into Human Neurodegeneration: Lessons Learnt From Drosophila

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Loss of spastic paraplegia gene atlastin induces age-dependent death of dopaminergic neurons in Drosophila

Cited by 36 publications

References 36 publications

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

The effects of ER morphology on synaptic structure and function in Drosophila melanogaster

Big Lessons from Tiny Flies:<em> Drosophila Melanogaster </em>as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems

Modeling Hereditary Spastic Paraplegias in Fruit Flies: Potential of Its Genetic Paraphernalia

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