期刊
JOURNAL OF CELL BIOLOGY
卷 219, 期 3, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201903135
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资金
- Wellcome Trust [096144, 209412, 091911, 107457]
- Medical Research Council/Engineering and Physical Sciences Research Council/Biotechnology and Biological Sciences Research Council next-generation imaging award
- University College London
- Leverhulme Trust
- National Institute of General Medical Sciences, National Institutes of Health [2P41GM103540]
- Marie Sklodowska-Curie Postdoctoral Fellowship
Memory and learning involve activity-driven expression of proteins and cytoskeletal reorganization at new synapses, requiring posttranscriptional regulation of localized mRNA a long distance from corresponding nuclei. A key factor expressed early in synapse formation is Msp300/Nesprin-1, which organizes actin filaments around the new synapse. How Msp300 expression is regulated during synaptic plasticity is poorly understood. Here, we show that activity-dependent accumulation of Msp300 in the postsynaptic compartment of the Drosophila larval neuromuscular junction is regulated by the conserved RNA binding protein Syncrip/hnRNP Q. Syncrip (Syp) binds to msp300 transcripts and is essential for plasticity. Single-molecule imaging shows that msp300 is associated with Syp in vivo and forms ribosome-rich granules that contain the translation factor eIF4E. Elevated neural activity alters the dynamics of Syp and the number of msp300:Syp:eIF4E RNP granules at the synapse, suggesting that these particles facilitate translation. These results introduce Syp as an important early acting activity-dependent regulator of a plasticity gene that is strongly associated with human ataxias.
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