{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Basak B"],"funding":["Department of Atomic Energy, Government of India","DBT/Wellcome Trust India Alliance"],"pagination":["bio057422"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7990853"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(3)"],"pubmed_abstract":["During phospholipase C-β (PLC-β) signalling in Drosophila photoreceptors, the phosphatidylinositol transfer protein (PITP) RDGB, is required for lipid transfer at endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (MCS). Depletion of RDGB or its mis-localization away from the ER-PM MCS results in multiple defects in photoreceptor function. Previously, the interaction between the FFAT motif of RDGB and the integral ER protein dVAP-A was shown to be essential for accurate localization to ER-PM MCS. Here, we report that the FFAT/dVAP-A interaction alone is insufficient to localize RDGB accurately; this also requires the function of the C-terminal domains, DDHD and LNS2. Mutations in each of these domains results in mis-localization of RDGB leading to loss of function. While the LNS2 domain is necessary, it is not sufficient for the correct localization of RDGB, which also requires the C-terminal DDHD domain. The function of the DDHD domain is mediated through an intramolecular interaction with the LNS2 domain. Thus, interactions between the additional domains in a multi-domain PITP together lead to accurate localization at the MCS and signalling function.This article has an associated First Person interview with the first author of the paper."],"journal":["Biology open"],"pubmed_title":["Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites."],"pmcid":["PMC7990853"],"funding_grant_id":["IA/S/14/2/501540"],"pubmed_authors":["Basak B","Raghu P","Krishnan H"],"additional_accession":[]},"is_claimable":false,"name":"Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites.","description":"During phospholipase C-β (PLC-β) signalling in Drosophila photoreceptors, the phosphatidylinositol transfer protein (PITP) RDGB, is required for lipid transfer at endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (MCS). Depletion of RDGB or its mis-localization away from the ER-PM MCS results in multiple defects in photoreceptor function. Previously, the interaction between the FFAT motif of RDGB and the integral ER protein dVAP-A was shown to be essential for accurate localization to ER-PM MCS. Here, we report that the FFAT/dVAP-A interaction alone is insufficient to localize RDGB accurately; this also requires the function of the C-terminal domains, DDHD and LNS2. Mutations in each of these domains results in mis-localization of RDGB leading to loss of function. While the LNS2 domain is necessary, it is not sufficient for the correct localization of RDGB, which also requires the C-terminal DDHD domain. The function of the DDHD domain is mediated through an intramolecular interaction with the LNS2 domain. Thus, interactions between the additional domains in a multi-domain PITP together lead to accurate localization at the MCS and signalling function.This article has an associated First Person interview with the first author of the paper.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2025-04-04T20:35:44.73Z","creation":"2025-04-04T20:35:44.73Z"},"accession":"S-EPMC7990853","cross_references":{"pubmed":["33597200"],"doi":["10.1242/bio.057422"]}}