TitleRNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration.
Publication TypeJournal Article
Year of Publication2018
AuthorsBakthavachalu B, Huelsmeier J, Sudhakaran IP, Hillebrand J, Singh A, Petrauskas A, Thiagarajan D, Sankaranarayanan M, Mizoue L, Anderson EN, Pandey UBhan, Ross E, VijayRaghavan K, Parker R, Ramaswami M
JournalNeuron
Volume98
Issue4
Pagination754-766.e4
Date Published2018 May 16
ISSN1097-4199
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.

DOI10.1016/j.neuron.2018.04.032
Alternate JournalNeuron
PubMed ID29772202