The dynamism of PABPN1 nuclear inclusions during the cell cycle

Neurobiol Dis. 2006 Sep;23(3):621-9. doi: 10.1016/j.nbd.2006.05.015. Epub 2006 Jul 24.

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is caused by expansion of a (GCN)10 to a (GCN)11-17 repeat coding for a polyalanine domain at the N-terminal part of poly(A) binding protein nuclear 1 (PABPN1). OPMD is characterized by the presence of intranuclear inclusions (INIs) in skeletal muscle fibers of patients. The formation of GFP-b13AlaPABPN1 INIs and their fate through the cell cycle were followed by time-lapse imaging. Our observations demonstrated that the GFP-b13AlaPABPN1 INIs are dynamic structures that can disassemble during mitosis. However, their presence in cells occasionally led to apoptosis. The length of the polyalanine tail or the overexpression of PABPN1 did not significantly affect the percentage of soluble PABPN1 in vitro. Moreover, overexpression of either the wild type (wt) or mutant (mut) forms of PABPN1 slowed down the cell proliferation. The slowing down of proliferation together with the occasional occurrence of apoptosis could contribute in vivo to the late onset of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Cycle / genetics*
  • Cell Line
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cell Nucleus / pathology
  • Cell Proliferation
  • Humans
  • Inclusion Bodies / genetics
  • Inclusion Bodies / metabolism*
  • Inclusion Bodies / pathology
  • Mitosis / genetics
  • Muscular Dystrophy, Oculopharyngeal / genetics
  • Muscular Dystrophy, Oculopharyngeal / metabolism*
  • Muscular Dystrophy, Oculopharyngeal / physiopathology
  • Mutation / genetics
  • Peptides / metabolism
  • Poly(A)-Binding Protein I / chemistry
  • Poly(A)-Binding Protein I / genetics
  • Poly(A)-Binding Protein I / metabolism*
  • Protein Structure, Tertiary / physiology

Substances

  • Peptides
  • Poly(A)-Binding Protein I
  • polyalanine