The phosphatidylinositol-transfer protein Nir2 binds phosphatidic acid and positively regulates phosphoinositide signalling

EMBO Rep. 2013 Oct;14(10):891-9. doi: 10.1038/embor.2013.113. Epub 2013 Jul 30.

Abstract

Phosphatidic acid (PA) and phosphoinositides are metabolically interconverted lipid second messengers that have central roles in many growth factor (GF)-stimulated signalling pathways. Yet, little is known about the mechanisms that coordinate their production and downstream signalling. Here we show that the phosphatidylinositol (PI)-transfer protein Nir2 translocates from the Golgi complex to the plasma membrane in response to GF stimulation. This translocation is triggered by PA formation and is mediated by its C-terminal region that binds PA in vitro. We further show that depletion of Nir2 substantially reduces the PI(4,5)P2 levels at the plasma membrane and concomitantly GF-stimulated PI(3,4,5)P3 production. Finally, we show that Nir2 positively regulates the MAPK and PI3K/AKT pathways. We propose that Nir2 through its PA-binding capability and PI-transfer activity can couple PA to phosphoinositide signalling, and possibly coordinates their local lipid metabolism and downstream signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Membrane / metabolism
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Phosphatidic Acids / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositols / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport / drug effects
  • Signal Transduction*

Substances

  • Calcium-Binding Proteins
  • Eye Proteins
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • PITPNM1 protein, human
  • Phosphatidic Acids
  • Phosphatidylinositols
  • Phosphatidylinositol 3-Kinases