Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites
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 re...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2021-03-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/10/3/bio057422 |
| _version_ | 1818900511566331904 |
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| author | Bishal Basak Harini Krishnan Padinjat Raghu |
| author_facet | Bishal Basak Harini Krishnan Padinjat Raghu |
| author_sort | Bishal Basak |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T20:05:01Z |
| format | Article |
| id | doaj.art-b050e5c6951645969f7169fc163edeba |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-19T20:05:01Z |
| publishDate | 2021-03-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-b050e5c6951645969f7169fc163edeba2022-12-21T20:07:31ZengThe Company of BiologistsBiology Open2046-63902021-03-0110310.1242/bio.057422057422Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sitesBishal Basak0Harini Krishnan1Padinjat Raghu2 Cellular Organization and Signalling, National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bengaluru 560065, India Cellular Organization and Signalling, National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bengaluru 560065, India Cellular Organization and Signalling, National Centre for Biological Sciences, TIFR-GKVK Campus, Bellary Road, Bengaluru 560065, India 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.http://bio.biologists.org/content/10/3/bio057422lipid transfer proteinmembrane contact sitesinter-domain interactionsphosphoinositidesdrosophila photoreceptors |
| spellingShingle | Bishal Basak Harini Krishnan Padinjat Raghu Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites Biology Open lipid transfer protein membrane contact sites inter-domain interactions phosphoinositides drosophila photoreceptors |
| title | Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites |
| title_full | Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites |
| title_fullStr | Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites |
| title_full_unstemmed | Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites |
| title_short | Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites |
| title_sort | interdomain interactions regulate the localization of a lipid transfer protein at er pm contact sites |
| topic | lipid transfer protein membrane contact sites inter-domain interactions phosphoinositides drosophila photoreceptors |
| url | http://bio.biologists.org/content/10/3/bio057422 |
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