A developmentally regulated, neuron-specific splice variant of the variable subunit Bbeta targets protein phosphatase 2A to mitochondria and modulates apoptosis. Academic Article uri icon

start page

  • 24976

end page

  • 24985

abstract

  • Heterotrimeric protein phosphatase 2A (PP2A) is a major Ser/Thr phosphatase composed of catalytic, structural, and regulatory subunits. Here, we characterize Bbeta2, a novel splice variant of the neuronal Bbeta regulatory subunit with a unique N-terminal tail. Bbeta2 is expressed predominantly in forebrain areas, and PP2A holoenzymes containing Bbeta2 are about 10-fold less abundant than those containing the Bbeta1 (previously Bbeta) isoform. Bbeta2 mRNA is dramatically induced postnatally and in response to neuronal differentiation of a hippocampal progenitor cell line. The divergent N terminus of Bbeta2 does not affect phosphatase activity but encodes a subcellular targeting signal. Bbeta2, but not Bbeta1 or an N-terminal truncation mutant, colocalizes with mitochondria in neuronal PC12 cells. Moreover, the Bbeta2 N-terminal tail is sufficient to target green fluorescent protein to this organelle. Inducible or transient expression of Bbeta2, but neither Bbeta1, Bgamma, nor a Bbeta2 mutant defective in holoenzyme formation, accelerates apoptosis in response to growth factor deprivation. Thus, alternative splicing of a mitochondrial localization signal generates a PP2A holoenzyme involved in neuronal survival signaling.

date/time value

  • 2003

Digital Object Identifier (DOI)

  • 10.1074/jbc.M302832200

PubMed Identifier

  • 12716901

volume

  • 278

number

  • 27

keywords

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Gene Expression Regulation, Developmental
  • Mitochondria
  • Molecular Sequence Data
  • Neurons
  • Organ Specificity
  • PC12 Cells
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • Rats
  • Signal Transduction