Anp32e/Cpd1 regulates protein phosphatase 2A activity at synapses during synaptogenesis

Eur J Neurosci. 2006 Jan;23(2):309-24. doi: 10.1111/j.1460-9568.2005.04555.x.


Anp32e/Cpd1, a member of the acidic nuclear phosphoprotein (Anp)32 family, is characterized by the presence of an amino terminal domain containing four leucine-rich repeats and a carboxyl-terminal low-compositional complexity acidic region. In previous studies performed to understand the biological role of Anp32e/Cpd1, we showed a predominant presence of Anp32e/Cpd1 in the nucleus. However, when Anp32e/Cpd1 is in the cytoplasm, it co-localizes spatially with protein phosphatase 2A (PP2A) near cell membranes, far from the synapses. In the present work, we show that Anp32e/Cpd1 is also present as a membrane-bound 74/76-kDa protein with a widespread distribution in the brain. We reveal that the expression, synthesis and half-life of this high-molecular-weight form of Anp32e/Cpd1 are spatially and temporally correlated with the cerebellar synaptogenesis period. We demonstrate that synaptic Anp32e/Cpd1 co-localizes, interacts and inhibits PP2A activity, and that phosphorylation of Anp32/Cpd1 is required for the Anp32e-PP2A interaction. Also, subcellular localization was shown with electronic microscopy. Finally, we examine Anp32e/Cpd1 and PP2A distribution in two ataxic mutant models, weaver and staggerer, and show that their co-localization in Purkinje cell dendrites depends on parallel fibre/Purkinje cell contacts. Based on these observations, we propose that Anp32e/Cpd1 mediates synaptogenesis process by modulating PP2A activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Blotting, Western / methods
  • Brain / cytology
  • Brain / growth & development*
  • Brain / metabolism
  • Gene Expression Regulation, Developmental / physiology*
  • Immunohistochemistry / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants
  • Microscopy, Immunoelectron / methods
  • Molecular Chaperones
  • Molecular Weight
  • Nerve Tissue Proteins / physiology*
  • Organogenesis
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Isoforms / metabolism
  • Protein Phosphatase 2
  • Subcellular Fractions / metabolism
  • Subcellular Fractions / ultrastructure
  • Synapses / metabolism*
  • Synapses / ultrastructure


  • Anp32e protein, mouse
  • Molecular Chaperones
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2