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Citation
Lee, S.B., Bagley, J.A., Lee, H.Y., Jan, L.Y., Jan, Y.N. (2011). Pathogenic polyglutamine proteins cause dendrite defects associated with specific actin cytoskeletal alterations in Drosophila.  Proc. Natl. Acad. Sci. U.S.A. 108(40): 16795--16800.
FlyBase ID
FBrf0216268
Publication Type
Research paper
Abstract

Whereas the neurodegeneration associated with various polyglutamine (polyQ) diseases has prompted extensive studies of polyQ-induced cell death, the neuronal loss that typically appears during late stages of the diseases may not account for the preceding movement and mental disorders. The cellular basis for polyQ-induced neuronal dysfunction preceding neuronal cell death remains largely unknown. Here we report defective dendrite morphogenesis within a specific subset of neurons due to polyQ toxicity that can be dissociated from caspase-dependent cell death. Expressing pathogenic spinocerebellar ataxia type 1 (SCA1) or type 3 (SCA3) proteins in Drosophila larval dendritic arborization neurons caused neuronal type-specific dendrite phenotypes primarily affecting terminal branches. We further show that expression of pathogenic polyQ proteins in adult flies after the formation of neuronal dendrites also greatly reduced dendritic complexity. These defects are associated with disruption of dendritic F-actin structures that can be partially mitigated by increasing Rac-PAK signaling. Together, these findings suggest that specific actin cytoskeletal alterations that alter dendrite morphology and function may contribute to the pathogenesis of at least a subset of polyQ disorders, including SCA3 and SCA1.

PubMed ID
PubMed Central ID
PMC3189048 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference
    Alleles (29)
    Genes (24)
    Human Disease Models (3)
    Insertions (2)
    Experimental Tools (1)
    Transgenic Constructs (27)
    Transcripts (1)