eprintid: 1473392 rev_number: 27 eprint_status: archive userid: 608 dir: disk0/01/47/33/92 datestamp: 2016-02-22 12:40:55 lastmod: 2021-11-30 00:36:10 status_changed: 2016-02-22 12:40:55 type: article metadata_visibility: show creators_name: Cockcroft, S creators_name: Garner, K creators_name: Yadav, S creators_name: Gomez-Espinoza, E creators_name: Raghu, P 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 ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G02 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) note: © 2016 Authors; published by Portland Press Limited. 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. date: 2016-02-15 official_url: http://dx.doi.org/10.1042/BST20150228 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1094858 doi: 10.1042/BST20150228 pii: BST20150228 lyricists_name: Cockcroft, Shamshad lyricists_id: SCOCK81 actors_name: Cockcroft, Shamshad actors_id: SCOCK81 actors_role: owner full_text_status: public publication: Biochemical Society Transactions volume: 44 number: 1 pagerange: 286-292 event_location: England issn: 1470-8752 citation: Cockcroft, S; Garner, K; Yadav, S; Gomez-Espinoza, E; Raghu, P; (2016) 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. Biochemical Society Transactions , 44 (1) pp. 286-292. 10.1042/BST20150228 <https://doi.org/10.1042/BST20150228>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1473392/1/biochem%20Soc%20trans%202015%20Review%20v13%20with%20Fig.pdf