TY - JOUR
T1 - RDGBα, a PtdIns-PtdOH transfer protein, regulates G-protein-coupled PtdIns(4,5)P2 signalling during Drosophila phototransduction
AU - Yadav, Shweta
AU - Garner, Kathryn
AU - Georgiev, Plamen
AU - Li, Michelle
AU - Gomez-Espinosa, Evelyn
AU - Panda, Aniruddha
AU - Mathre, Swarna
AU - Okkenhaug, Hanneke
AU - Cockcroft, Shamshad
AU - Raghu, Padinjat
N1 - Funding information: This work was supported by project grants from the Wellcome Trust to P.R. and S.C.; from the Biotechnology and Biological Sciences Research Council to S.C.; and the National Centre for Biological Sciences-TIFR and the Wellcome Trust-DBT India Alliance to P.R. We thank the British Heart Foundation for PhD studentships to K.G. and to E.G.-E.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
KW - RDGB
KW - Lipid transfer
KW - Phosphoinositide
KW - PITP
UR - https://www.scopus.com/pages/publications/84946064699
U2 - 10.1242/jcs.173476
DO - 10.1242/jcs.173476
M3 - Article
SN - 0021-9533
VL - 128
SP - 3330
EP - 3344
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 17
ER -