title: RdgBα reciprocally transfers PA and PI at ER-PM contact sites to maintain PI(4,5)P2 homoeostasis during phospholipase C signalling in Drosophila photoreceptors.
abstract: Phosphatidylinositol (PI) is the precursor lipid for the synthesis of PI 4,5-bisphosphate [PI(4,5)P2] at the plasma membrane (PM) and is sequentially phosphorylated by the lipid kinases, PI 4-kinase and phosphatidylinositol 4-phosphate (PI4P)-5-kinase. Receptor-mediated hydrolysis of PI(4,5)P2 takes place at the PM but PI resynthesis occurs at the endoplasmic reticulum (ER). Thus PI(4,5)P2 resynthesis requires the reciprocal transport of two key intermediates, phosphatidic acid (PA) and PI between the ER and the PM. PI transfer proteins (PITPs), defined by the presence of the PITP domain, can facilitate lipid transfer between membranes; the PITP domain comprises a hydrophobic cavity with dual specificity but accommodates a single phospholipid molecule. The class II PITP, retinal degeneration type B (RdgB)α is a multi-domain protein and its PITP domain can bind and transfer PI and PA. In Drosophila photoreceptors, a well-defined G-protein-coupled phospholipase Cβ (PLCβ) signalling pathway, phototransduction defects resulting from loss of RdgBα can be rescued by expression of the PITP domain provided it is competent for both PI and PA transfer. We propose that RdgBα proteins maintain PI(4,5)P2 homoeostasis after PLC activation by facilitating the reciprocal transport of PA and PI at ER-PM membrane contact sites.
authors: Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, U.K. s.cockcroft@ucl.ac.uk.
authors: Shamshad
authors: S
authors: Cockcroft
authors: Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, U.K.
authors: Kathryn
authors: K
authors: Garner
authors: Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, U.K.
authors: Shweta
authors: S
authors: Yadav
authors: Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, U.K.
authors: Evelyn
authors: E
authors: Gomez-Espinoza
authors: Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, U.K.
authors: Padinjat
authors: P
authors: Raghu
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D002462:Cell Membrane / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism*; D006706:Homeostasis; D055537:Light Signal Transduction; D008565:Membrane Proteins / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; C068848:rdgB protein, Drosophila; D010738:Type C Phospholipases
keywords: 5-bisphosphate [PI(4,5)P2]; endoplasmic reticulum–plasma membrane (ER—PM) contact sites; phosphatidic acid; phosphatidic acid (PA) transport proteins; phosphatidylinositol; phosphatidylinositol 4; phosphatidylinositol transfer protein (PITP); phospholipase C; phototransduction; retinal degeneration type B (RdgB)