Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes
Cell surface receptors control how cells respond to their environment. Many cell surface receptors recycle from endosomes to the plasma membrane via a recently discovered pathway, which includes sorting-nexin SNX17, Retriever, WASH, and CCC complexes. Here, using mammalian cells, we discover that PI...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/69709 |
| _version_ | 1811203047732281344 |
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| author | Sai Srinivas Panapakkam Giridharan Guangming Luo Pilar Rivero-Rios Noah Steinfeld Helene Tronchere Amika Singla Ezra Burstein Daniel D Billadeau Michael A Sutton Lois S Weisman |
| author_facet | Sai Srinivas Panapakkam Giridharan Guangming Luo Pilar Rivero-Rios Noah Steinfeld Helene Tronchere Amika Singla Ezra Burstein Daniel D Billadeau Michael A Sutton Lois S Weisman |
| author_sort | Sai Srinivas Panapakkam Giridharan |
| collection | DOAJ |
| description | Cell surface receptors control how cells respond to their environment. Many cell surface receptors recycle from endosomes to the plasma membrane via a recently discovered pathway, which includes sorting-nexin SNX17, Retriever, WASH, and CCC complexes. Here, using mammalian cells, we discover that PIKfyve and its upstream PI3-kinase VPS34 positively regulate this pathway. VPS34 produces phosphatidylinositol 3-phosphate (PI3P), which is the substrate for PIKfyve to generate PI3,5P2. We show that PIKfyve controls recycling of cargoes including integrins, receptors that control cell migration. Furthermore, endogenous PIKfyve colocalizes with SNX17, Retriever, WASH, and CCC complexes on endosomes. Importantly, PIKfyve inhibition results in displacement of Retriever and CCC from endosomes. In addition, we show that recruitment of SNX17 is an early step and requires VPS34. These discoveries suggest that VPS34 and PIKfyve coordinate an ordered pathway to regulate recycling from endosomes and suggest how PIKfyve functions in cell migration. |
| first_indexed | 2024-04-12T02:48:41Z |
| format | Article |
| id | doaj.art-7c35c8cb7b114934a237748c8f78a216 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:48:41Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7c35c8cb7b114934a237748c8f78a2162022-12-22T03:51:04ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.69709Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomesSai Srinivas Panapakkam Giridharan0https://orcid.org/0000-0002-6214-0397Guangming Luo1https://orcid.org/0000-0003-1234-3388Pilar Rivero-Rios2Noah Steinfeld3Helene Tronchere4Amika Singla5Ezra Burstein6https://orcid.org/0000-0003-4341-6367Daniel D Billadeau7Michael A Sutton8https://orcid.org/0000-0003-1593-727XLois S Weisman9https://orcid.org/0000-0001-7740-9785Life Sciences Institute and Department of Cellular and Developmental Biology, University of Michigan, Ann Arbor, United StatesLife Sciences Institute and Department of Cellular and Developmental Biology, University of Michigan, Ann Arbor, United StatesLife Sciences Institute and Department of Cellular and Developmental Biology, University of Michigan, Ann Arbor, United StatesLife Sciences Institute and Department of Cellular and Developmental Biology, University of Michigan, Ann Arbor, United StatesINSERM U1048 I2MC, France and Université Paul Sabatier, Toulouse, FranceDepartment of Internal Medicine, and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Internal Medicine, and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United StatesDivision of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, United StatesNeuroscience Graduate Program, Molecular and Behavioral Neuroscience Institute, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, United StatesLife Sciences Institute and Department of Cellular and Developmental Biology, University of Michigan, Ann Arbor, United StatesCell surface receptors control how cells respond to their environment. Many cell surface receptors recycle from endosomes to the plasma membrane via a recently discovered pathway, which includes sorting-nexin SNX17, Retriever, WASH, and CCC complexes. Here, using mammalian cells, we discover that PIKfyve and its upstream PI3-kinase VPS34 positively regulate this pathway. VPS34 produces phosphatidylinositol 3-phosphate (PI3P), which is the substrate for PIKfyve to generate PI3,5P2. We show that PIKfyve controls recycling of cargoes including integrins, receptors that control cell migration. Furthermore, endogenous PIKfyve colocalizes with SNX17, Retriever, WASH, and CCC complexes on endosomes. Importantly, PIKfyve inhibition results in displacement of Retriever and CCC from endosomes. In addition, we show that recruitment of SNX17 is an early step and requires VPS34. These discoveries suggest that VPS34 and PIKfyve coordinate an ordered pathway to regulate recycling from endosomes and suggest how PIKfyve functions in cell migration.https://elifesciences.org/articles/69709phosphatidylinositol 3,5-bisphosphateRetrieverrecyclingSNX17membrane traffic |
| spellingShingle | Sai Srinivas Panapakkam Giridharan Guangming Luo Pilar Rivero-Rios Noah Steinfeld Helene Tronchere Amika Singla Ezra Burstein Daniel D Billadeau Michael A Sutton Lois S Weisman Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes eLife phosphatidylinositol 3,5-bisphosphate Retriever recycling SNX17 membrane traffic |
| title | Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes |
| title_full | Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes |
| title_fullStr | Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes |
| title_full_unstemmed | Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes |
| title_short | Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes |
| title_sort | lipid kinases vps34 and pikfyve coordinate a phosphoinositide cascade to regulate retriever mediated recycling on endosomes |
| topic | phosphatidylinositol 3,5-bisphosphate Retriever recycling SNX17 membrane traffic |
| url | https://elifesciences.org/articles/69709 |
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