Characterizing the in vivo pathogenicity of Vps35-D620N in Drosophila

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dc.contributor.advisor Rodal, Avital
dc.contributor.author Narayanan, Krishna
dc.date.accessioned 2017-05-12T19:28:21Z
dc.date.available 2017-05-12T19:28:21Z
dc.date.issued 2017 en
dc.identifier.uri http://hdl.handle.net/10192/33820
dc.description.abstract The Retromer trafficking complex sorts endosomal cargo, driving recycling from the lysosomal degradation pathway. The D620N mutation in the core Retromer subunit, Vps35, is a cause of the late-onset, autosomal dominant form of Parkinson’s Disease. Using Drosophila to study the in vivo effects of the mutant protein, Vps35-D620N, we can better understand the role of Vps35 in neuronal growth and morphology and its role in Parkinson’s Disease. However, previously described Vps35-D620N phenotypes in Drosophila may be an artifact of the GAL4-UAS overexpression system that was used to introduce the mutant protein into the neurons of the animal. We generated flies with an endogenous knock-in of Vps35-D620N. Here, we perform lifespan, larval locomotion, and bouton counting assays to study the in vivo pathogenicity of the endogenous mutant. The endogenous Vps35-D620N flies show a slight lifespan phenotype and no dramatic reduction in larval locomotion, but the endogenous mutant protein leads to synaptic overgrowth at the NMJ akin to phenotypes observed in nwk null mutants and vps35 loss of function mutants. We conclude that future experiments should be directed towards determining if the synaptic overgrowth correlates with increased pMad levels and defective F-actin polymerization. en
dc.language.iso en en
dc.rights Copyright by Krishna Narayanan 2017 en
dc.title Characterizing the in vivo pathogenicity of Vps35-D620N in Drosophila en
dc.type Thesis
dc.contributor.department Undergraduate Program in Biology en


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