RRC ID 57199
著者 Bakthavachalu B, Huelsmeier J, Sudhakaran IP, Hillebrand J, Singh A, Petrauskas A, Thiagarajan D, Sankaranarayanan M, Mizoue L, Anderson EN, Pandey UB, Ross E, VijayRaghavan K, Parker R, Ramaswami M.
タイトル RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration.
ジャーナル Neuron
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.
巻・号 98(4)
ページ 754-766.e4
公開日 2018-5-16
DOI 10.1016/j.neuron.2018.04.032
PII S0896-6273(18)30340-4
PMID 29772202
MeSH Amyotrophic Lateral Sclerosis / genetics Animals Ataxin-2 / genetics* Ataxin-2 / metabolism C9orf72 Protein Cytoplasmic Granules / metabolism* Drosophila Drosophila Proteins / genetics* Drosophila Proteins / metabolism Fertility Heterogeneous-Nuclear Ribonucleoprotein Group F-H Intrinsically Disordered Proteins / genetics* Intrinsically Disordered Proteins / metabolism Memory, Long-Term* Neurodegenerative Diseases / genetics* Ribonucleoproteins / metabolism* Smell Spinocerebellar Ataxias / genetics Survival
IF 14.403
引用数 25
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