Relocalization of the polypyrimidine tract-binding protein during PKA-induced neurite growth

Biochim Biophys Acta. 2007 Jun;1773(6):912-23. doi: 10.1016/j.bbamcr.2007.02.006. Epub 2007 Feb 22.

Abstract

Neurite RNA binding proteins are important for neurite growth, a process critical for neuronal development and regeneration after injury. It has been known that many RNA binding proteins undergo nucleocytoplasmic shuttling but how their nucleocytoplasmic distributions are regulated during neurite growth has not been well explored. Here we found that the polypyrimidine tract binding protein (PTB) was exported from the nucleus and accumulated at growing neurite terminals upon activation of the PKA pathway in PC12 cells in a PKA-target Ser16-dependent manner. RNA interference (RNAi) of PTB significantly disrupted the neurite growth. We then examined the role of cytoplasmic PTB in relation to mRNAs involved in neurite growth. We found that PTB was preferentially associated with the beta-actin mRNA transcripts in cytoplasmic fractions. RNAi of PTB reduced neurite accumulation of the endogenous actin proteins. It is thus likely that, during PKA-induced neurite growth, PTB is relocalized through Ser16 phosphorylation to the cytoplasm where it is associated with beta-actin mRNA and is critical for the mRNA localization to neurites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cytoplasm / metabolism*
  • Neurites / enzymology*
  • PC12 Cells
  • Phosphorylation
  • Polypyrimidine Tract-Binding Protein / antagonists & inhibitors
  • Polypyrimidine Tract-Binding Protein / genetics
  • Polypyrimidine Tract-Binding Protein / metabolism*
  • Protein Processing, Post-Translational / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Rats

Substances

  • Actins
  • RNA, Messenger
  • RNA, Small Interfering
  • Polypyrimidine Tract-Binding Protein
  • Cyclic AMP-Dependent Protein Kinases