RRC ID 11545
Author Kanuka H, Hiratou T, Igaki T, Kanda H, Kuranaga E, Sawamoto K, Aigaki T, Okano H, Miura M.
Title Gain-of-function screen identifies a role of the Sec61alpha translocon in Drosophila postmitotic neurotoxicity.
Journal Biochim. Biophys. Acta
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.
Volume 1726(3)
Pages 225-37
Published 2005-11-30
DOI 10.1016/j.bbagen.2005.06.020
PII S0304-4165(05)00183-2
PMID 16243437
MeSH Animals Cell Death* Cell Line Drosophila / cytology Drosophila / genetics* Drosophila / metabolism Drosophila Proteins / genetics Drosophila Proteins / physiology* Endoplasmic Reticulum / metabolism Eye / cytology Genetic Complementation Test Membrane Proteins / genetics Membrane Proteins / physiology* Membrane Transport Proteins Mitosis Models, Biological Mutagenesis Neurons / cytology* Photoreceptor Cells, Invertebrate / cytology Protein Transport SEC Translocation Channels Saccharomyces cerevisiae Proteins / genetics
IF 3.438
Times Cited 12