Forgetting is regulated via Musashi-mediated translational control of the Arp2/3 complex

Cell. 2014 Mar 13;156(6):1153-1166. doi: 10.1016/j.cell.2014.01.054.


A plastic nervous system requires the ability not only to acquire and store but also to forget. Here, we report that musashi (msi-1) is necessary for time-dependent memory loss in C. elegans. Tissue-specific rescue demonstrates that MSI-1 function is necessary in the AVA interneuron. Using RNA-binding protein immunoprecipitation (IP), we found that MSI-1 binds to mRNAs of three subunits of the Arp2/3 actin branching regulator complex in vivo and downregulates ARX-1, ARX-2, and ARX-3 translation upon associative learning. The role of msi-1 in forgetting is also reflected by the persistence of learning-induced GLR-1 synaptic size increase in msi-1 mutants. We demonstrate that memory length is regulated cooperatively through the activation of adducin (add-1) and by the inhibitory effect of msi-1. Thus, a GLR-1/MSI-1/Arp2/3 pathway induces forgetting and represents a novel mechanism of memory decay by linking translational control to the structure of the actin cytoskeleton in neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics*
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Interneurons / metabolism*
  • Memory*
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Biosynthesis
  • RNA, Helminth / metabolism*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Sequence Alignment
  • Synapses


  • Actin-Related Protein 2-3 Complex
  • Actins
  • Caenorhabditis elegans Proteins
  • Nerve Tissue Proteins
  • RNA, Helminth
  • RNA, Messenger
  • RNA-Binding Proteins
  • msi-1 protein, C elegans