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Citation
Kanuka, H., Hiratou, T., Igaki, T., Kanda, H., Kuranaga, E., Sawamoto, K., Aigaki, T., Okano, H., Miura, M. (2005). Gain-of-function screen identifies a role of the Sec61alpha translocon in Drosophila postmitotic neurotoxicity.  Biochim. Biophys. Acta 1726(3): 225--237.
FlyBase ID
FBrf0189853
Publication Type
Research paper
Abstract

To elucidate the intrinsic mechanisms of neurotoxicity induction, including those underlying neural cell death and neurodegeneration, we developed a gain-of-function screen for gene products causing neural cell loss. To identify novel genes with a cell-death-related function in neurons, we screened 4,964 Drosophila GS lines, in which one or two genes from much of the Drosophila genome can be overexpressed. Approximately 0.68% of the GS lines produced phenotypes involving a loss of postmitotic neurons. Of these, we identified and characterized the endd2 gene, which encodes the Drosophila ortholog of Sec61alpha (DSec61alpha), an endoplasmic reticulum protein with protein translocation activity. Ectopic expression of DSec61alpha caused neural cell death accompanied by the accumulation of ubiquitinated proteins, which was mediated by DSec61alpha's translocon activity. This supported our previous observation that the DSec61alpha translocon contributes to expanded polyglutamine-mediated neuronal toxicity, which is also associated with ubiquitinated protein accumulation. These data suggest that the translocon may be a novel component of neural cell death and degeneration pathways. Our approach can be used to identify potential neurotoxic factors within the whole genome, which will increase our understanding of the molecular mechanisms of various types of cell death, including those associated with human neurodegenerative diseases.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Biochim. Biophys. Acta
    Title
    Biochimica et Biophysica Acta
    Publication Year
    1947-
    ISBN/ISSN
    0006-3002
    Data From Reference
    Alleles (50)
    Genes (36)
    Natural transposons (1)
    Insertions (36)
    Experimental Tools (1)
    Transgenic Constructs (11)