Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells

PLoS One. 2009 Sep 15;4(9):e7031. doi: 10.1371/journal.pone.0007031.

Abstract

Lipin-1 is a protein that has dual functions as a phosphatidic acid phosphohydrolase (PAP) and a nuclear transcriptional coactivator. It remains unknown how the nuclear localization and coactivator functions of lipin-1 are regulated. Here, we show that lipin-1 (including both the alpha and beta isoforms) is modified by sumoylation at two consensus sumoylation sites. We are unable to detect sumoylation of the related proteins lipin-2 and lipin-3. Lipin-1 is sumoylated at relatively high levels in brain, where lipin-1alpha is the predominant form. In cultured embryonic cortical neurons and SH-SY5Y neuronal cells, ectopically expressed lipin-1alpha is localized in both the nucleus and the cytoplasm, and the nuclear localization is abrogated by mutating the consensus sumyolation motifs. The sumoylation site mutant of lipin-1alpha loses the capacity to coactivate the transcriptional (co-) activators PGC-1alpha and MEF2, consistent with its nuclear exclusion. Thus, these results show that sumoylation facilitates the nuclear localization and transcriptional coactivator behavior of lipin-1alpha that we observe in cultured neuronal cells, and suggest that lipin-1alpha may act as a sumoylation-regulated transcriptional coactivator in brain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Brain / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • Mice
  • Microscopy, Fluorescence / methods
  • Neurons / metabolism*
  • Nuclear Proteins / metabolism*
  • Phosphatidate Phosphatase
  • SUMO-1 Protein / metabolism*
  • Transcription, Genetic

Substances

  • Nuclear Proteins
  • SUMO-1 Protein
  • SUMO1 protein, human
  • LPIN1 protein, human
  • Lpin1 protein, mouse
  • Phosphatidate Phosphatase