Piezo1 Is Required for Myoblast Migration and Involves Polarized Clustering in Association with Cholesterol and GM1 Ganglioside
A specific plasma membrane distribution of the mechanosensitive ion channel Piezo1 is required for cell migration, but the mechanism remains elusive. Here, we addressed this question using WT and <i>Piezo1</i>-silenced C2C12 mouse myoblasts and WT and <i>Piezo1</i>-KO human k...
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MDPI AG
2023-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/24/2784 |
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| author | Juliette Vanderroost Thibaud Parpaite Noémie Avalosse Patrick Henriet Christophe E. Pierreux Joseph H. Lorent Philippe Gailly Donatienne Tyteca |
| author_facet | Juliette Vanderroost Thibaud Parpaite Noémie Avalosse Patrick Henriet Christophe E. Pierreux Joseph H. Lorent Philippe Gailly Donatienne Tyteca |
| author_sort | Juliette Vanderroost |
| collection | DOAJ |
| description | A specific plasma membrane distribution of the mechanosensitive ion channel Piezo1 is required for cell migration, but the mechanism remains elusive. Here, we addressed this question using WT and <i>Piezo1</i>-silenced C2C12 mouse myoblasts and WT and <i>Piezo1</i>-KO human kidney HEK293T cells. We showed that cell migration in a cell-free area and through a porous membrane decreased upon <i>Piezo1</i> silencing or deletion, but increased upon Piezo1 activation by Yoda1, whereas migration towards a chemoattractant gradient was reduced by Yoda1. Piezo1 organized into clusters, which were preferentially enriched at the front. This polarization was stimulated by Yoda1, accompanied by Ca<sup>2+</sup> polarization, and abrogated by partial cholesterol depletion. Piezo1 clusters partially colocalized with cholesterol- and GM1 ganglioside-enriched domains, the proportion of which was increased by Yoda1. Mechanistically, Piezo1 activation induced a differential mobile fraction of GM1 associated with domains and the bulk membrane. Conversely, cholesterol depletion abrogated the differential mobile fraction of Piezo1 associated with clusters and the bulk membrane. In conclusion, we revealed, for the first time, the differential implication of Piezo1 depending on the migration mode and the interplay between GM1/cholesterol-enriched domains at the front during migration in a cell-free area. These domains could provide the optimal biophysical properties for Piezo1 activity and/or spatial dissociation from the PMCA calcium efflux pump. |
| first_indexed | 2024-03-08T20:54:22Z |
| format | Article |
| id | doaj.art-10372010d4fc40468ca324efa4dbff45 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T20:54:22Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-10372010d4fc40468ca324efa4dbff452023-12-22T13:59:35ZengMDPI AGCells2073-44092023-12-011224278410.3390/cells12242784Piezo1 Is Required for Myoblast Migration and Involves Polarized Clustering in Association with Cholesterol and GM1 GangliosideJuliette Vanderroost0Thibaud Parpaite1Noémie Avalosse2Patrick Henriet3Christophe E. Pierreux4Joseph H. Lorent5Philippe Gailly6Donatienne Tyteca7de Duve Institute, UCLouvain, 1200 Brussels, BelgiumInstitute of Neuroscience, UCLouvain, 1200 Brussels, Belgiumde Duve Institute, UCLouvain, 1200 Brussels, Belgiumde Duve Institute, UCLouvain, 1200 Brussels, Belgiumde Duve Institute, UCLouvain, 1200 Brussels, BelgiumLouvain Drug Research Institute, UCLouvain, 1200 Brussels, BelgiumInstitute of Neuroscience, UCLouvain, 1200 Brussels, Belgiumde Duve Institute, UCLouvain, 1200 Brussels, BelgiumA specific plasma membrane distribution of the mechanosensitive ion channel Piezo1 is required for cell migration, but the mechanism remains elusive. Here, we addressed this question using WT and <i>Piezo1</i>-silenced C2C12 mouse myoblasts and WT and <i>Piezo1</i>-KO human kidney HEK293T cells. We showed that cell migration in a cell-free area and through a porous membrane decreased upon <i>Piezo1</i> silencing or deletion, but increased upon Piezo1 activation by Yoda1, whereas migration towards a chemoattractant gradient was reduced by Yoda1. Piezo1 organized into clusters, which were preferentially enriched at the front. This polarization was stimulated by Yoda1, accompanied by Ca<sup>2+</sup> polarization, and abrogated by partial cholesterol depletion. Piezo1 clusters partially colocalized with cholesterol- and GM1 ganglioside-enriched domains, the proportion of which was increased by Yoda1. Mechanistically, Piezo1 activation induced a differential mobile fraction of GM1 associated with domains and the bulk membrane. Conversely, cholesterol depletion abrogated the differential mobile fraction of Piezo1 associated with clusters and the bulk membrane. In conclusion, we revealed, for the first time, the differential implication of Piezo1 depending on the migration mode and the interplay between GM1/cholesterol-enriched domains at the front during migration in a cell-free area. These domains could provide the optimal biophysical properties for Piezo1 activity and/or spatial dissociation from the PMCA calcium efflux pump.https://www.mdpi.com/2073-4409/12/24/2784lipid domainscalcium live cell imagingFura-2 polarizationlipid lateral diffusionPiezo1 KO cellsmechanosensitive channels |
| spellingShingle | Juliette Vanderroost Thibaud Parpaite Noémie Avalosse Patrick Henriet Christophe E. Pierreux Joseph H. Lorent Philippe Gailly Donatienne Tyteca Piezo1 Is Required for Myoblast Migration and Involves Polarized Clustering in Association with Cholesterol and GM1 Ganglioside Cells lipid domains calcium live cell imaging Fura-2 polarization lipid lateral diffusion Piezo1 KO cells mechanosensitive channels |
| title | Piezo1 Is Required for Myoblast Migration and Involves Polarized Clustering in Association with Cholesterol and GM1 Ganglioside |
| title_full | Piezo1 Is Required for Myoblast Migration and Involves Polarized Clustering in Association with Cholesterol and GM1 Ganglioside |
| title_fullStr | Piezo1 Is Required for Myoblast Migration and Involves Polarized Clustering in Association with Cholesterol and GM1 Ganglioside |
| title_full_unstemmed | Piezo1 Is Required for Myoblast Migration and Involves Polarized Clustering in Association with Cholesterol and GM1 Ganglioside |
| title_short | Piezo1 Is Required for Myoblast Migration and Involves Polarized Clustering in Association with Cholesterol and GM1 Ganglioside |
| title_sort | piezo1 is required for myoblast migration and involves polarized clustering in association with cholesterol and gm1 ganglioside |
| topic | lipid domains calcium live cell imaging Fura-2 polarization lipid lateral diffusion Piezo1 KO cells mechanosensitive channels |
| url | https://www.mdpi.com/2073-4409/12/24/2784 |
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