Aplysia CPEB can form prion-like multimers in sensory neurons that contribute to long-term facilitation

Cell. 2010 Feb 5;140(3):421-35. doi: 10.1016/j.cell.2010.01.008.

Abstract

Prions are proteins that can assume at least two distinct conformational states, one of which is dominant and self-perpetuating. Previously we found that a translation regulator CPEB from Aplysia, ApCPEB, that stabilizes activity-dependent changes in synaptic efficacy can display prion-like properties in yeast. Here we find that, when exogenously expressed in sensory neurons, ApCPEB can form an amyloidogenic self-sustaining multimer, consistent with it being a prion-like protein. In addition, we find that conversion of both the exogenous and the endogenous ApCPEB to the multimeric state is enhanced by the neurotransmitter serotonin and that an antibody that recognizes preferentially the multimeric ApCPEB blocks persistence of synaptic facilitation. These results are consistent with the idea that ApCPEB can act as a self-sustaining prion-like protein in the nervous system and thereby might allow the activity-dependent change in synaptic efficacy to persist for long periods of time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / metabolism
  • Animals
  • Aplysia / metabolism*
  • Long-Term Potentiation
  • Polylysine / metabolism
  • Prions / chemistry
  • Prions / metabolism*
  • Sensory Receptor Cells / metabolism
  • Serotonin / metabolism
  • Synapses / metabolism
  • mRNA Cleavage and Polyadenylation Factors / chemistry
  • mRNA Cleavage and Polyadenylation Factors / metabolism*

Substances

  • Amyloid
  • Prions
  • mRNA Cleavage and Polyadenylation Factors
  • Polylysine
  • Serotonin