Lysophosphatidylinositol-acyltransferase-1 is involved in cytosolic Ca2+ oscillations in macrophages

Abstract

Lysophosphatidylinositol-acyltransferase-1 (LPIAT1) specifically catalyzes the transfer of arachidonoyl-CoA to lysophosphoinositides. LPIAT^-/- mice have been shown to have severe defects in the brain and liver; however, the exact molecular mechanisms behind these conditions are not well understood. As immune cells have been implicated in liver inflammation based on disfunction of LPIAT1, we generated Raw264.7 macrophages deficient in LPIAT1, using shRNA and CRISPR/Cas9. The amount of C38:4 species in phosphoinositides, especially in PtdInsP₂ , was remarkably decreased in these cells. Unlike in wild-type cells, LPIAT1-deficient cells showed prolonged oscillations of intracellular Ca²⁺ upon UDP stimulation, which is known to activate phospholipase Cβ through the Gq-coupled P2Y6 receptor, even in the absence of extracellular Ca²⁺ . It is speculated that the prolonged Ca²⁺ response may be relevant to the increased risk of liver inflammation induced by LPIAT1 disfunction.

Keywords: Ca2+ oscillation; arachidonic acid; lysophosphatidylinositol-acyltransferase-1 (MBOAT7); phosphatidylinositol (4,5)P2; phosphoinositides.