Phosphoinositide phosphatase Sac3 regulates the cell surface expression of scavenger receptor A and formation of lipid droplets in macrophages

Exp Cell Res. 2017 Aug 15;357(2):252-259. doi: 10.1016/j.yexcr.2017.05.022. Epub 2017 May 25.

Abstract

The findings of this study suggest that the phosphoinositide phosphatase Sac3 maintains the protein level of scavenger receptor A (SR-A) and regulates foam cell formation. RAW264.7 macrophages were transfected with short hairpin RNAs that target Sac3. The knockdown decreased the level of the cell surface SR-A and suppressed the acetylated low density lipoprotein-induced foam cell formation. The associated regulator of PIKfyve (ArPIKfyve) is a scaffold protein that protects Sac3 from proteasome-dependent degradation. The knockdown of ArPIKfyve decreased Sac3, cell surface SR-A, and foam cell formation. The knockdown of PIKfyve had no effect on SR-A protein levels. These results suggest that the ArPIKfyve-Sac3 complex regulates SR-A protein levels independently of its effect on PIKfyve activity.

Keywords: ArPIKfyve; Foam cell formation; PIKfyve; SR-A; Sac3.

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Flavoproteins / genetics
  • Flavoproteins / metabolism*
  • Gene Knockdown Techniques / methods
  • Humans
  • Lipid Droplets / metabolism*
  • Macrophages / metabolism*
  • Mice
  • Phosphoinositide Phosphatases / genetics
  • Phosphoinositide Phosphatases / metabolism*
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • RAW 264.7 Cells
  • Receptors, Scavenger / metabolism*
  • Scavenger Receptors, Class A / metabolism

Substances

  • Flavoproteins
  • Receptors, Scavenger
  • Scavenger Receptors, Class A
  • FIG4 protein, human
  • Phosphoric Monoester Hydrolases
  • Fig4 protein, mouse
  • Phosphoinositide Phosphatases