title: RDGBα, a PtdIns-PtdOH transfer protein, regulates G-protein-coupled PtdIns(4,5)P2 signalling during Drosophila phototransduction.
abstract: 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.
authors.affiliation: National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bangalore, Karnataka 560065, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Yadav
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College, London WC1E 6JJ, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Garner
authors.affiliation: Inositide Laboratory, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Plamen
authors.initials: P
authors.lastname: Georgiev
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College, London WC1E 6JJ, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College, London WC1E 6JJ, UK.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Gomez-Espinosa
authors.affiliation: National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bangalore, Karnataka 560065, India Manipal University, Madhav Nagar, Manipal, Karnataka 576104, India.
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Panda
authors.affiliation: National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bangalore, Karnataka 560065, India Manipal University, Madhav Nagar, Manipal, Karnataka 576104, India.
authors.forename: Swarna
authors.initials: S
authors.lastname: Mathre
authors.affiliation: Inositide Laboratory, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Okkenhaug
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College, London WC1E 6JJ, UK s.cockcroft@ucl.ac.uk praghu@ncbs.res.in.
authors.forename: Shamshad
authors.initials: S
authors.lastname: Cockcroft
authors.affiliation: National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bangalore, Karnataka 560065, India Inositide Laboratory, Babraham Institute, Cambridge CB22 3AT, UK s.cockcroft@ucl.ac.uk praghu@ncbs.res.in.
authors.forename: Padinjat
authors.initials: P
authors.lastname: Raghu
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D055537:Light Signal Transduction / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000235:genetics / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; C068848:rdgB protein, Drosophila; D010738:Type C Phospholipases
keywords: Lipid transfer; PITP; Phosphoinositide; RDGB