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Bakthavachalu, B., Huelsmeier, J., Sudhakaran, I.P., Hillebrand, J., Singh, A., Petrauskas, A., Thiagarajan, D., Sankaranarayanan, M., Mizoue, L., Anderson, E.N., Pandey, U.B., Ross, E., VijayRaghavan, K., Parker, R., Ramaswami, M. (2018). RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration.  Neuron 98(4): 754--766.e4.
FlyBase ID
FBrf0238947
Publication Type
Research paper
Abstract
Human Ataxin-2 is implicated in the cause and progression of amyotrophic lateral sclerosis (ALS) and type 2 spinocerebellar ataxia (SCA-2). In Drosophila, a conserved atx2 gene is essential for animal survival as well as for normal RNP-granule assembly, translational control, and long-term habituation. Like its human homolog, Drosophila Ataxin-2 (Atx2) contains polyQ repeats and additional intrinsically disordered regions (IDRs). We demonstrate that Atx2 IDRs, which are capable of mediating liquid-liquid phase transitions in vitro, are essential for efficient formation of neuronal mRNP assemblies in vivo. Remarkably, ΔIDR mutants that lack neuronal RNP granules show normal animal development, survival, and fertility. However, they show defects in long-term memory formation/consolidation as well as in C9ORF72 dipeptide repeat or FUS-induced neurodegeneration. Together, our findings demonstrate (1) that higher-order mRNP assemblies contribute to long-term neuronal plasticity and memory, and (2) that a targeted reduction in RNP-granule formation efficiency can alleviate specific forms of neurodegeneration.
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Related Publication(s)
Note
Ataxin-2 Is Droppin' Some Knowledge.
Becker and Gitler, 2018, Neuron 98(4): 673--675 [FBrf0239003]
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neuron
    Title
    Neuron
    Publication Year
    1988-
    ISBN/ISSN
    0896-6273
    Data From Reference