Importin-7 mediates memory consolidation through regulation of nuclear translocation of training-activated MAPK in Drosophila

Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3072-7. doi: 10.1073/pnas.1520401113. Epub 2016 Feb 29.

Abstract

Translocation of signaling molecules, MAPK in particular, from the cytosol to nucleus represents a universal key element in initiating the gene program that determines memory consolidation. Translocation mechanisms and their behavioral impact, however, remain to be determined. Here, we report that a highly conserved nuclear transporter, Drosophila importin-7 (DIM-7), regulates import of training-activated MAPK for consolidation of long-term memory (LTM). We show that silencing DIM-7 functions results in impaired LTM, whereas overexpression of DIM-7 enhances LTM. This DIM-7-dependent regulation of LTM is confined to a consolidation time window and in mushroom body neurons. Image data show that bidirectional alteration in DIM-7 expression results in proportional changes in the intensity of training-activated MAPK accumulated within the nuclei of mushroom body neurons during LTM consolidation. Such DIM-7-regulated nuclear accumulation of activated MAPK is observed only in the training specified for LTM induction and determines the amplitude, but not the time course, of memory consolidation.

Keywords: Drosophila; MAPK; consolidation; importin; long-term memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Butadienes / pharmacology
  • Cell Nucleus / metabolism*
  • Cycloheximide / pharmacology
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / physiology*
  • Enzyme Activation
  • Gene Expression Regulation / drug effects
  • Genes, Reporter
  • Hot Temperature
  • Karyopherins / biosynthesis
  • Karyopherins / deficiency
  • Karyopherins / genetics
  • Karyopherins / physiology*
  • MAP Kinase Signaling System*
  • Memory Consolidation / drug effects
  • Memory Consolidation / physiology*
  • Memory, Long-Term / drug effects
  • Memory, Long-Term / physiology*
  • Memory, Short-Term / physiology
  • Mifepristone / pharmacology
  • Mitogen-Activated Protein Kinases / metabolism
  • Mushroom Bodies / cytology
  • Mushroom Bodies / physiology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Nitriles / pharmacology
  • Recombinant Fusion Proteins / metabolism
  • Smell / physiology
  • Time Factors

Substances

  • Butadienes
  • Drosophila Proteins
  • Karyopherins
  • Msk protein, Drosophila
  • Nitriles
  • Recombinant Fusion Proteins
  • U 0126
  • Mifepristone
  • Cycloheximide
  • Mitogen-Activated Protein Kinases