The ER tether VAPA is required for proper cell motility and anchors ER-PM contact sites to focal adhesions
Cell motility processes highly depend on the membrane distribution of Phosphoinositides, giving rise to cytoskeleton reshaping and membrane trafficking events. Membrane contact sites serve as platforms for direct lipid exchange and calcium fluxes between two organelles. Here, we show that VAPA, an E...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2024-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/85962 |
| _version_ | 1797271771132461056 |
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| author | Hugo Siegfried Georges Farkouh Rémi Le Borgne Catherine Pioche-Durieu Thaïs De Azevedo Laplace Agathe Verraes Lucien Daunas Jean-Marc Verbavatz Mélina L Heuzé |
| author_facet | Hugo Siegfried Georges Farkouh Rémi Le Borgne Catherine Pioche-Durieu Thaïs De Azevedo Laplace Agathe Verraes Lucien Daunas Jean-Marc Verbavatz Mélina L Heuzé |
| author_sort | Hugo Siegfried |
| collection | DOAJ |
| description | Cell motility processes highly depend on the membrane distribution of Phosphoinositides, giving rise to cytoskeleton reshaping and membrane trafficking events. Membrane contact sites serve as platforms for direct lipid exchange and calcium fluxes between two organelles. Here, we show that VAPA, an ER transmembrane contact site tether, plays a crucial role during cell motility. CaCo2 adenocarcinoma epithelial cells depleted for VAPA exhibit several collective and individual motility defects, disorganized actin cytoskeleton and altered protrusive activity. During migration, VAPA is required for the maintenance of PI(4)P and PI(4,5)P2 levels at the plasma membrane, but not for PI(4)P homeostasis in the Golgi and endosomal compartments. Importantly, we show that VAPA regulates the dynamics of focal adhesions (FA) through its MSP domain, is essential to stabilize and anchor ventral ER-PM contact sites to FA, and mediates microtubule-dependent FA disassembly. To conclude, our results reveal unknown functions for VAPA-mediated membrane contact sites during cell motility and provide a dynamic picture of ER-PM contact sites connection with FA mediated by VAPA. |
| first_indexed | 2024-03-07T14:13:02Z |
| format | Article |
| id | doaj.art-c53c03f4ba7e4a009a3a45fe87d4aff5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-07T14:13:02Z |
| publishDate | 2024-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c53c03f4ba7e4a009a3a45fe87d4aff52024-03-06T14:18:46ZengeLife Sciences Publications LtdeLife2050-084X2024-03-011310.7554/eLife.85962The ER tether VAPA is required for proper cell motility and anchors ER-PM contact sites to focal adhesionsHugo Siegfried0Georges Farkouh1Rémi Le Borgne2Catherine Pioche-Durieu3https://orcid.org/0000-0003-0988-1169Thaïs De Azevedo Laplace4Agathe Verraes5Lucien Daunas6Jean-Marc Verbavatz7Mélina L Heuzé8https://orcid.org/0000-0002-4271-2706Université Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, F-75013, Paris, FranceCell motility processes highly depend on the membrane distribution of Phosphoinositides, giving rise to cytoskeleton reshaping and membrane trafficking events. Membrane contact sites serve as platforms for direct lipid exchange and calcium fluxes between two organelles. Here, we show that VAPA, an ER transmembrane contact site tether, plays a crucial role during cell motility. CaCo2 adenocarcinoma epithelial cells depleted for VAPA exhibit several collective and individual motility defects, disorganized actin cytoskeleton and altered protrusive activity. During migration, VAPA is required for the maintenance of PI(4)P and PI(4,5)P2 levels at the plasma membrane, but not for PI(4)P homeostasis in the Golgi and endosomal compartments. Importantly, we show that VAPA regulates the dynamics of focal adhesions (FA) through its MSP domain, is essential to stabilize and anchor ventral ER-PM contact sites to FA, and mediates microtubule-dependent FA disassembly. To conclude, our results reveal unknown functions for VAPA-mediated membrane contact sites during cell motility and provide a dynamic picture of ER-PM contact sites connection with FA mediated by VAPA.https://elifesciences.org/articles/85962cell migrationmembrane contact sitescell adhesionlipid traffickingphosphoinositidesendoplasmic reticulum |
| spellingShingle | Hugo Siegfried Georges Farkouh Rémi Le Borgne Catherine Pioche-Durieu Thaïs De Azevedo Laplace Agathe Verraes Lucien Daunas Jean-Marc Verbavatz Mélina L Heuzé The ER tether VAPA is required for proper cell motility and anchors ER-PM contact sites to focal adhesions eLife cell migration membrane contact sites cell adhesion lipid trafficking phosphoinositides endoplasmic reticulum |
| title | The ER tether VAPA is required for proper cell motility and anchors ER-PM contact sites to focal adhesions |
| title_full | The ER tether VAPA is required for proper cell motility and anchors ER-PM contact sites to focal adhesions |
| title_fullStr | The ER tether VAPA is required for proper cell motility and anchors ER-PM contact sites to focal adhesions |
| title_full_unstemmed | The ER tether VAPA is required for proper cell motility and anchors ER-PM contact sites to focal adhesions |
| title_short | The ER tether VAPA is required for proper cell motility and anchors ER-PM contact sites to focal adhesions |
| title_sort | er tether vapa is required for proper cell motility and anchors er pm contact sites to focal adhesions |
| topic | cell migration membrane contact sites cell adhesion lipid trafficking phosphoinositides endoplasmic reticulum |
| url | https://elifesciences.org/articles/85962 |
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