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Citation
Muñoz-Soriano, V., Paricio, N. (2007). Overexpression of Septin 4, the Drosophila homologue of human CDCrel-1, is toxic for dopaminergic neurons.  Europ. J. Neurosci. 26(11): 3150--3158.
FlyBase ID
FBrf0200746
Publication Type
Research paper
Abstract

parkin loss-of-function mutations are linked to autosomal recessive juvenile parkinsonism. Parkin is an E3 ubiquitin ligase that promotes degradation of specific target proteins by the proteasome. It has been proposed that loss of Parkin activity will result in accumulation of its substrates, thus leading to dopaminergic (DA) neuron death. In Drosophila, parkin mutations cause degeneration of a subset of DA neurons in the brain but no Parkin substrates have yet been described. Here we characterized the septin 4 gene, which encodes the Drosophila orthologue of human CDCrel-1, a Parkin substrate. We showed that Septin 4 overexpression causes age-dependent disruption of DA neuron integrity in the dorsomedial cluster, which is suppressed by coexpression of Parkin and enhanced by reducing parkin function. Furthermore, other phenotypes caused by Septin 4 overexpression are also enhanced in a heterozygous parkin mutant background. This indicates that Septin 4 accumulation is toxic for DA neurons and suggests that Septin 4 could be a genuine substrate of Drosophila Parkin. Regarding this, we also showed that both proteins are able to interact physically with each other in vitro, thus supporting this hypothesis.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Europ. J. Neurosci.
    Title
    European Journal of Neuroscience
    Publication Year
    1989-
    ISBN/ISSN
    0953-816X
    Data From Reference
    Aberrations (1)
    Alleles (11)
    Genes (5)
    Physical Interactions (1)
    Natural transposons (1)
    Insertions (2)
    Experimental Tools (1)
    Transgenic Constructs (9)