RDGBα, a PtdIns-PtdOH transfer protein, regulates G-protein-coupled PtdIns(4,5)P2 signalling during Drosophila phototransduction

J Cell Sci. 2015 Sep 1;128(17):3330-44. doi: 10.1242/jcs.173476. Epub 2015 Jul 22.


Many membrane receptors activate phospholipase C (PLC) during signalling, triggering changes in the levels of several plasma membrane lipids including phosphatidylinositol (PtdIns), phosphatidic acid (PtdOH) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. It is widely believed that exchange of lipids between the plasma membrane and endoplasmic reticulum (ER) is required to restore lipid homeostasis during PLC signalling, yet the mechanism remains unresolved. RDGBα (hereafter RDGB) is a multi-domain protein with a PtdIns transfer protein (PITP) domain (RDGB-PITPd). We find that, in vitro, the RDGB-PITPd binds and transfers both PtdOH and PtdIns. In Drosophila photoreceptors, which experience high rates of PLC activity, RDGB function is essential for phototransduction. We show that binding of PtdIns to RDGB-PITPd is essential for normal phototransduction; however, this property is insufficient to explain the in vivo function because another Drosophila PITP (encoded by vib) that also binds PtdIns cannot rescue the phenotypes of RDGB deletion. In RDGB mutants, PtdIns(4,5)P2 resynthesis at the plasma membrane following PLC activation is delayed and PtdOH levels elevate. Thus RDGB couples the turnover of both PtdIns and PtdOH, key lipid intermediates during G-protein-coupled PtdIns(4,5)P2 turnover.

Keywords: Lipid transfer; PITP; Phosphoinositide; RDGB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Light Signal Transduction / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Phosphatidic Acids / genetics
  • Phosphatidic Acids / metabolism*
  • Phosphatidylinositol 4,5-Diphosphate / genetics
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Type C Phospholipases / genetics
  • Type C Phospholipases / metabolism*


  • Drosophila Proteins
  • Eye Proteins
  • Membrane Proteins
  • Phosphatidic Acids
  • Phosphatidylinositol 4,5-Diphosphate
  • rdgB protein, Drosophila
  • Type C Phospholipases